Search Results
within category "Congenital & Chromosomal Abnormalities"
Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Hyperpolarized Imaging for New Treatments (HyPOINT)
The introduction of triple combination CFTR modulator therapy for patients with Cystic
Fibrosis (CF) with at least one copy of the deltaF508 mutation is expected to provide major
health benefits, but will also require novel outcome measures that can detect CF lung disease
at an early stage, capture the efficacy of new therapies when disease manifestations are
limited, as well as determine whether stopping existing chronic maintenance therapies does
not have negative effects.
In the past decade, research has focused on the multiple breath washout (MBW) test, as a
sensitive outcome measure, especially if highly-effective modulator therapies are initiated
in early childhood. Even LCI, however, may not adequately capture early lung function
changes, thus warranting investigation of even more sensitive outcome measures.
Magnetic resonance imaging (MRI) has the advantage of being a radiation-free modality, making
it more suitable for assessing response to therapy in a shorter time frame with repeated
imaging. Inhalation of a hyperpolarized gas enables the visualization and quantification of
regional ventilation in the lung and can be combined with structural MRI to assess both
structure and function in parallel.
The main Investigator and others have recently formed an international consortium (the 129Xe
MRI Clinical Trial Consortium), comprised of both imaging experts and pulmonary clinicians to
standardize imaging procedures, thus facilitating multi-site implementations. Data from this
proposed study (HyPOINT; Hyperpolarized Imaging for New Treatments) will inform the future
utility of MRI for both longitudinal studies to track disease progression over time as well
as for future interventional trials. Further, the current study could inform the design of
future trials of interventions of patients for whom currently no effective CFTR modulator
therapy is available and for patients with rare genotypes thus laying the groundwork for a
more personalized medicine approach in the near-term future.
Michael Rock, MD
All
6 Years to 18 Years old
Phase 4
This study is NOT accepting healthy volunteers
NCT04259970
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Inclusion Criteria:
1. Written informed consent (and assent when applicable) obtained from subject or
subject's legal representative.
2. Willingness and ability to adhere to the study visit schedule and other protocol
requirements.
3. Documentation of a CF diagnosis as evidenced by one or more clinical features
consistent with the CF phenotype and one or more of the following criteria:
1. Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine
iontophoresis test
2. Two well-characterized mutations in the cystic fibrosis transmembrane conductance
regulator (CFTR) gene
4. Phase 1 only: Age 6 to 18 years, inclusive, at the time of consent.
5. Phase 2 only: Ages 9 to 18 years, inclusive, at the time of consent.
6. Clinically stable with no acute antibiotic usage in the 14 days prior to the first
visit.
7. Genotype with F508del on at least one allele.
8. No change in chronic pulmonary medications or therapies in the 28 days prior to the
first visit.
9. Stable CFTR modulator therapy (TEZ/IVA or LUM/IVA) for at least 28 days prior to the
first visit or currently not receiving CFTR modulator therapy.
10. Ability to cooperate with MRI procedures.
11. Phase 1 only: FEV1 greater than or equal to 80% predicted based on GLI reference
equations.
Exclusion Criteria:
1. Standard MRI exclusions (Metal implants, claustrophobia).
2. For females of childbearing potential: Positive urine pregnancy test at Screening or
Visit 1 or Lactating.
3. Any other condition that, in the opinion of the Site Investigator/designee, would
preclude informed consent or assent, make study participation unsafe, complicate
interpretation of study outcome data, or otherwise interfere with achieving the study
objectives.
Long-term Follow-up Study of Patients Receiving Onasemnogene Abeparvovec-xioi
This is a long-term follow-up safety and efficacy study of participants in clinical trials
for spinal muscular atrophy (SMA) who were treated with onasemnogene abeparvovec-xioi.
Participants will roll over from their respective previous (parent) study into this long-term
study for continuous monitoring of safety as well as monitoring of continued efficacy and
durability of response to onasemnogene abeparvovec-xioi treatment.
Jennifer Kwon, MD
All
Not specified
Phase 4
This study is NOT accepting healthy volunteers
NCT04042025
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Inclusion Criteria:
• Any participant with SMA who received onasemnogene abeparvovec-xioi gene replacement
therapy in an Novartis Gene Therapies, Inc. sponsored clinical study
• Participant/parent/legal guardian willing and able to complete the informed consent
process and comply with study procedures and visit schedule
Exclusion Criteria:
• Parent/legal guardian unable or unwilling to participate in the long-term follow-up
safety study
Spinal muscular atrophy, Congenital & Chromosomal Abnormalities, Spinal Muscular Atrophy Type I, Spinal Muscular Atrophy Type II, Spinal Muscular Atrophy Type III, SMA
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to
children by their health care provider, act in the bodies of children and young adults in
hopes to find the most safe and effective dose for children. The primary objective of this
study is to evaluate the PK of understudied drugs currently being administered to children
per SOC as prescribed by their treating provider.
Maria Stanley
All
up to 20 Years old
NA
This study is also accepting healthy volunteers
NCT04278404
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Inclusion Criteria:
1. Participant is < 21 years of age
2. Parent/ Legal Guardian/ Adult Participant can understand the consent process and is
willing to provide informed consent/HIPAA:
3. (a) Participant is receiving one or more of the study drugs of interest at the time of
enrollment or (b) Participant is NOT receiving one or more of the study drugs of
interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
1. Participant has a known pregnancy Below exclusion criteria apply only to participants
receiving one or more of the study drugs of interest at the time of enrollment,
2. Has had intermittent dialysis within previous 24 hours
3. Has had a kidney transplant within previous 30 days
4. Has had a liver transplant within previous 1 year
5. Has had a stem cell transplant within previous 1 year
6. Has had therapeutic hypothermia within previous 24 hours
7. Has had plasmapheresis within the previous 24 hours
8. Has a Ventricular Assist Device
9. Has any condition which would make the participant, in the opinion of the
investigator, unsuitable for the study
CHaractErizing CFTR Modulated Changes in Sweat Chloride and Their Association With Clinical Outcomes (CHEC-SC)
This is a multicenter, cross-sectional, cohort study which will collect contemporary sweat
chloride (SC) values from approximately 5000 Cystic Fibrosis (CF) patients prescribed and
currently receiving commercially approved Cystic Fibrosis transmembrane conductance regulator
(CFTR) modulator therapies.
Michael Rock, MD
All
4 Months and over
NA
This study is NOT accepting healthy volunteers
NCT03350828
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Inclusion Criteria:
1. Written informed consent (and assent when applicable) obtained from subject or
subject's legal representative
2. Enrolled in the CFFPR
3. Male or female ≥ 4 months of age on day of study visit
4. Diagnosis of CF.
5. Current treatment with a prescribed commercially approved CFTR modulator for at least
90 days prior to enrollment
6. Able to perform the testing and procedures required for this study, as judged by the
investigator
Additional Inclusion Criteria for CHEC-PKPD Sub-Study:
1. Male or female ≥ 6 years of age on day of study visit.
2. Current treatment with elexacaftor/tezacaftor/ivacaftor for at least 90 days prior to
enrollment.
3. Last dose of elexacaftor/tezacaftor/ivacaftor taken at least 24hours and last dose of
ivacaftor taken at least 12 hours prior to trough blood draw on day of visit.
Exclusion Criteria:
1. Presence of a condition or abnormality that, in the opinion of the Investigator, would
compromise the safety of the patient or the quality of the data
2. Currently enrolled in an investigational trial (including open-label follow-on studies
and Early Access Programs (EAP) of an agent expected to have an impact on sweat
chloride (refer to current list provided on study website)
A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation
This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an
observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in
subjects with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have
an approved Ivacaftor-Responsive mutation
Michael Rock, MD
All
up to 24 Months old
Phase 3
This study is NOT accepting healthy volunteers
NCT03277196
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Inclusion Criteria:
Ivacaftor Arm: Subjects From Study 124 (NCT02725567 ) Part B:
• Subjects transitioning from Study 124 Part B must have completed the last study visit
of Study 124 Part B.
• As judged by the investigator, parent or legal guardian must be able to understand
protocol requirements, restrictions, and instructions; and must sign the informed
consent form (ICF).
Ivacaftor Arm: Subjects Not From Study 124 Part B:
• Confirmed diagnosis of CF, or 2 CF-causing mutations.
• An ivacaftor- responsive CFTR mutation on at least 1 allele. Subjects will be eligible
in countries/regions where ivacaftor is approved for use in subjects 2 years of age
and older.
• As judged by the investigator, parent or legal guardian must be able to understand
protocol requirements, restrictions, and instructions; and must sign the ICF.
Observational Arm:
• Received ivacaftor treatment in Study 124 Part B and elected not to enroll or
ineligible to enroll in the ivacaftor arm of Study 126.
Exclusion Criteria:
Ivacaftor Arm: Subjects From Study 124 Part B:
• History of any illness or condition that, in the opinion of the investigator, might
confound the results of the study or pose an additional risk in administering
ivacaftor to the subject.
• Subjects receiving commercially available ivacaftor treatment
Ivacaftor Arm: Subjects Not From Study 124 Part B:
• History of any illness or condition that, in the opinion of the investigator, might
confound the results of the study or pose an additional risk in administering
ivacaftor to the subject
• An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes
in therapy for pulmonary disease within 4 weeks of Day 1
• Abnormal liver function at screening
• Hemoglobin <9.5 g/dL at screening
• History of solid organ or hematological transplantation
• Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1
Observational Arm:
• Receiving ivacaftor treatment
Other protocol defined Inclusion/Exclusion criteria may apply.
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
This phase III trial studies how well blinatumomab works in combination with chemotherapy in
treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or
B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as
blinatumomab, may induce changes in the body's immune system and may interfere with the
ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine,
dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine,
mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to
stop the growth of cancer cells, either by killing the cells, by stopping them from dividing,
or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate.
Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving
blinatumomab and combination chemotherapy may work better than combination chemotherapy alone
in treating patients with B-ALL. This trial also assigns patients into different chemotherapy
treatment regimens based on risk (the chance of cancer returning after treatment). Treating
patients with chemotherapy based on risk may help doctors decide which patients can best
benefit from which chemotherapy treatment regimens.
Kenneth Desantes, M.D.
All
365 Days to 31 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT03914625
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Inclusion Criteria:
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening
(Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement
for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or
without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL
(performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell
count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on
a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis
can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL
circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without
Down syndrome.
• Note: For B-LLy patients with tissue available for flow cytometry, the criterion
for diagnosis should be analogous to B-ALL. For tissue processed by other means
(i.e., paraffin blocks), the methodology and criteria for immunophenotypic
analysis to establish the diagnosis of B-LLy defined by the submitting
institution will be accepted (diagnostic biopsy for B-LLy must be performed
within 14 days prior to enrollment).
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Exclusion Criteria:
• Patient must not have secondary ALL that developed after treatment of a prior
malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior
history of transient myeloproliferative disease (TMD) are not considered to have had a
prior malignancy. They would therefore be eligible whether or not the TMD was treated
with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to
initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion
criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in
the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to
initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV
steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to
the start of systemic protocol therapy.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for
APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted
containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be
known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the
DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior
to administration of any systemic or intrathecal chemotherapy, except for steroid
pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular
disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, the following additional exclusion criteria apply:
• T-Lymphoblastic Lymphoma.
• Morphologically unclassifiable lymphoma.
• Absence of both B-cell and T-cell phenotype markers in a case submitted as
lymphoblastic lymphoma.
• CNS positive disease or testicular involvement.
• M2 (5% •25% blasts) or M3 (> 25% blasts) marrow.
• Patients with known Charcot-Marie-Tooth disease.
• Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
regardless of blast immunophenotype.
• Patients requiring radiation at diagnosis.
• Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs. A pregnancy test is required for female
patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation.
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Down Syndrome, Non-Hodgkin's Lymphoma, Lymphoid Leukemia, Leukemia, other, Leukemia, Lymphoma
Project: Every Child for Younger Patients With Cancer
This study gathers health information for the Project: Every Child for younger patients with
cancer. Gathering health information over time from younger patients with cancer may help
doctors find better methods of treatment and on-going care.
Kenneth Desantes, M.D.
All
up to 25 Years old
N/A
This study is NOT accepting healthy volunteers
NCT02402244
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Inclusion Criteria:
• Enrollment must occur within 6 months of initial disease presentation OR within 6
months of refractory disease, disease progression, disease recurrence, second or
secondary malignancy, or post-mortem
• Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome,
Registry and Future Contact components of APEC14B1 any time after they reach age of
majority
• Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent
or young adult populations are eligible for enrollment as follows:
• All cancer cases with an International Classification of Diseases for Oncology
(ICD-O) histologic behavior code of two "2" (carcinoma in situ) or three "3"
(malignant)
• All neoplastic lesions of the central nervous system regardless of behavior,
i.e., benign, borderline or malignant
• The following other benign/borderline conditions:
• Mesoblastic nephroma
• Teratomas (mature and immature types)
• Myeloproliferative diseases including transient myeloproliferative disease
• Langerhans cell histiocytosis
• Lymphoproliferative diseases
• Desmoid tumors
• Gonadal stromal cell tumors
• Subjects must be =< 25 years of age at time of original diagnosis, except for patients
who are being screened specifically for eligibility onto a COG (or COG participating
National Clinical Trials Network [NCTN]) therapeutic study, for which there is a
higher upper age limit
• All patients or their parents or legally authorized representatives must sign a
written informed consent and agree to participate in at least one component of the
study; parents will be asked to sign a separate consent for their own biospecimen
submission
• If patients or their parents or legally authorized representatives have not
signed the Part A subject consent form at the time of a diagnostic bone marrow
procedure, it is recommended that they initially provide consent for drawing
extra bone marrow using the Consent for Collection of Additional Bone Marrow;
consent using the Part A subject consent form must be provided prior to any other
procedures for eligibility screening or banking under APEC14B1
Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Lymphoproliferative Disorder, Malignant Solid Neoplasm, Myeloproliferative Neoplasm, Stromal Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
This research trial studies kidney tumors in younger patients. Collecting and storing samples
of tumor tissue, blood, and urine from patients with cancer to study in the laboratory may
help doctors learn more about changes that occur in deoxyribonucleic acid (DNA) and identify
biomarkers related to cancer.
Kenneth Desantes, M.D.
All
up to 29 Years old
N/A
This study is NOT accepting healthy volunteers
NCT00898365
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Inclusion Criteria:
• Patients with the first occurrence of any tumor of the kidney identified on CT scan or
MRI are eligible for this study; histologic diagnosis is not required prior to
enrollment but is required for all patients once on study
• Eligible tumors include (but are not limited to):
• Nephroblastic tumors
• Nephroblastoma (Wilms' tumor) (favorable histology, anaplasia [diffuse,
focal])
• Nephrogenic rests and nephroblastomatosis
• Cystic nephroma and cystic partially differentiated nephroblastoma
• Metanephric tumors (metanephric adenoma, metanephric adenofibroma,
metanephric stromal tumor)
• Mesoblastic nephroma (cellular, classic, mixed)
• Clear cell sarcoma
• Rhabdoid tumor (any malignant rhabdoid tumor occurring outside the central
nervous system [CNS])
• Renal epithelioid tumors of childhood (papillary renal cell carcinoma, medullary
renal cell carcinoma, renal tumors associated with Xp11.2 translocations,
oncocytic renal neoplasms after neuroblastoma)
• Angiolipoma
• Ossifying renal tumor of infancy
• Patients with the first occurrence of the following tumors are also eligible:
• Extrarenal nephroblastoma or extrarenal neprogenic rests
• Malignant rhabdoid tumor occurring anywhere outside the central nervous system
• Required specimens, reports, forms, and copies of imaging studies must be available or
will become available for submission and the institution must intend on submitting
them as described in the protocol procedures
• For ALL patients, (with exception of bilateral, bilaterally predisposed, multicentric,
or unilateral tumor in solitary kidney planning to enroll without biopsy***), the
following submissions are required:
• A complete set of recut hematoxylin and eosin (H & E) slides (including from
sampled lymph nodes, if patient had upfront nephrectomy)
• * Tissue must be from diagnosis, prior to any renal tumor directed
chemotherapy or radiation (only exception is for presumed favorable
histology Wilms tumor [FHWT] patients discovered to have diffuse anaplastic
Wilms tumor [DAWT] at delayed nephrectomy and plan to enroll at delayed
nephrectomy)
• Representative formalin-fixed paraffin-embedded tissue block or if a block is
unavailable, 10 unstained slides from a representative block of tumor, if
available.
• Tissue must be from diagnosis, prior to any renal tumor directed
chemotherapy or radiation (only exception is for presumed FHWT patients
discovered to have DAWT at delayed nephrectomy and plan to enroll at delayed
nephrectomy)
• Institutional pathology report, Specimen Transmittal Form, and Pre-Treatment
Pathology Checklist
• Copies of images and institutional reports of CT and/or MRI abdomen and pelvis,
and Pre Treatment Imaging Checklist
• Copies of images and institutional report of chest CT for all malignant tumors
• Institutional surgical report(s) and Pre-Treatment Surgical Checklist
• CRFs: Staging Checklist and Metastatic Disease Form (if metastatic disease is
noted on imaging)
• Patients with bilateral, bilaterally predisposed, multicentric, or
unilateral tumor in solitary kidney planning to enroll without biopsy via
imaging only •these patients will not have central review or have a risk
assignment issued, but may contribute to specimen banking for future
research. However, if biopsy is done, tissue must be submitted as for other
renal tumors, and initial risk assignment will require pathology and
surgical rapid central reviews. The Specimen Transmittal Form and Pre
Treatment Pathology Checklist are also needed.
• Please note: if the above required items are not received within 120 days of
study enrollment, the patient will be considered off study
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
Dyskeratosis congenita is a disease that affects numerous parts of the body, most typically
causing failure of the blood system. Lung disease, liver disease and cancer are other
frequent causes of illness and death. Bone marrow transplantation (BMT) can cure the blood
system but can make the lung and liver disease and risk of cancer worse, because of DNA
damaging agents such as alkylators and radiation that are typically used in the procedure.
Based on the biology of DC, we hypothesize that it may be possible to avoid these DNA
damaging agents in patients with DC, and still have a successful BMT. In this protocol we
will test whether a regimen that avoids DNA alkylators and radiation can permit successful
BMT without compromising survival in patients with DC.
Inga Hofmann, M.D.
All
up to 65 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT01659606
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Inclusion Criteria:
• Bone marrow hypocellular for age
• Moderate or severe aplastic anemia defined by one of the following: peripheral blood
neutrophils < 0.5 x 10^9/L; platelets < 30 x 10^9/L or platelet transfusion
dependence; reticulocytes < 50 x 10^9/L in anemic patients or red cell transfusion
dependence
• Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin
pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence
of two or more associated features; OR a pathogenic mutation in DKC1,TERC, TERT,
NOP10, NHP2, TCAB1, TINF2, CTC1, PARN, RTEL1, ACD, NAF1, STN1, or ZCCHC8, as reported
by a CLIA-approved laboratory; OR age-adjusted mean telomere length < 1%ile in
peripheral blood lymphocytes as reported by a CLIA-approved laboratory; OR
Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome
• Availability of a related or unrelated donor with a 7/8 or 8/8 match for HLA-A, B, C,
and DRB1.
• Patient and/or legal guardian must be able to sign informed consent.
• Donor must provide a marrow allograft.
• Diagnosis of Fanconi anemia must be excluded by mitomycin C or diepoxybutane
chromosomal breakage testing on peripheral blood at a CLIA-approved laboratory (not
required for patients with a genetic mutation consistent with DC)
• Adequate renal function with glomerular filtration rate equal to or greater than 30
ml/min/1.73 m2
Exclusion Criteria:
• Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow
examination.
• Karnofsky/Lansky performance status < 40.
• Uncontrolled bacterial, viral or fungal infections.
• Positive test for the human immunodeficiency virus (HIV).
• Pregnancy or breastfeeding.
• Known severe or life-threatening allergy or intolerance to fludarabine, alemtuzumab,
mycophenolate mofetil or both cyclosporine and tacrolimus.
• Positive patient anti-donor HLA antibody, which is deemed clinically significant.
• Prior allogeneic marrow or stem cell transplantation.
• Prior solid organ transplantation.
Dyskeratosis Congenita, Hoyeraal Hreidarsson Syndrome, Revesz Syndrome, Aplastic Anemia, Other Hematopoietic, Hematologic cancers, other
X-linked Hypophosphatemia Disease Monitoring Program
The objectives of this observational study are to characterize XLH disease presentation and
progression and to assess long-term effectiveness and safety of burosumab.
Neil Paloian
All
Not specified
III/IV
This study is NOT accepting healthy volunteers
NCT03651505
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Inclusion Criteria:
• Willing and able to provide informed consent or, in the case of patients under the age
of 18 years (or 16 years, depending on the region), provide assent (if required) and
informed consent by a legally authorized representative after the nature of the study
has been explained, and prior to any research-related procedures.
• Clinical diagnosis of XLH based on family history, OR confirmed PHEX mutation, OR
biochemical profile consistent with XLH.
• Willing and able to comply with the study visit schedule and study procedures.
Exclusion Criteria:
• Concurrent enrollment in an Ultragenyx-sponsored clinical trial is NOT permitted.
• Serious medical or psychiatric comorbidity.
• Less than one year of life expectancy.
This study is continued evaluation of the safety and probable benefit of the Flourish
Pediatric Esophageal Atresia device through the Humanitarian Device Exemption (HDE) pathway.
Charles Leys
All
up to 12 Months old
This study is NOT accepting healthy volunteers
NCT03615495
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Inclusion Criterion:
• Patient treated for esophageal atresia with Flourish device starting May 12, 2017
Other diseases of esophagus, Children's & Adolescent Health, Digestive Health & Liver Disease, Esophageal Atresia, Digestive System Abnormalities, Esophageal Disorders Congenital
A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation
The purpose of this study is to evaluate the safety of ivacaftor treatment, and PK of
ivacaftor and metabolites in subjects with cystic fibrosis (CF) who are <24 months of age at
treatment initiation and have an ivacaftor-responsive CF transmembrane conductance regulator
(CFTR) gene mutation.
Michael Rock, MD
All
up to 24 Months old
Phase 3
This study is NOT accepting healthy volunteers
NCT02725567
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Inclusion Criteria:
• Confirmed diagnosis of CF by sweat chloride value or CF mutation criteria.
• Have 1 of the following 10 CFTR mutations on at least 1 allele: G551D, G178R, S549N,
S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H (eligible in regions where
ivacaftor is approved for use). Part A/B group may also have other
ivacaftor-responsive mutations.
• Hematology, serum chemistry, and vital signs results at screening with no clinically
significant abnormalities that would interfere with the study assessments, as judged
by the investigator.
Exclusion Criteria:
• History of any illness or condition that, in the opinion of the investigator, might
confound the results of the study or pose an additional risk in administering study
drug to the subject
• Colonization with organisms associated with a more rapid decline in pulmonary status
at screening (Only for Parts A and B)
• History of abnormal liver function or abnormal liver function at screening
• History of solid organ or hematological transplantation
• Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A
within 2 weeks before Day 1
• Participation in a clinical study involving administration of either an
investigational or a marketed drug within 30 days or 5 terminal half-lives before
screening
• Hemoglobin (Hgb) <9.5 g/dL at screening
• Chronic kidney disease of Stage 3 or above
• Presence of a non-congenital or progressive lens opacity or cataract at Screening
Other protocol defined Inclusion/Exclusion Criteria may apply.
Impact of Discontinuing Chronic Therapies in People With Cystic Fibrosis on Highly Effective CFTR Modulator Therapy (SIMPLIFY)
Despite the increasingly common use of cystic fibrosis transmembrane conductance regulator
(CFTR) modulator therapies in treating CF, it is still largely unknown whether or not other
chronic therapies can be safely stopped. The SIMPLIFY study is being done to test whether or
not it is safe to stop taking inhaled hypertonic saline or Pulmozyme® (dornase alfa) in those
people that are also taking Trikafta™.
Trikafta (elexacaftor/tezacaftor/ivacaftor) is a combination CFTR modulator therapy that was
approved by the Food and Drug Administration for people with CF who have at least one F508del
mutation. The three drugs that make up Trikafta work together to allow many more chloride
ions to move into and out of the cells, improving the balance of salt and water in the lungs.
These changes result in better clearance of mucus from the lungs and improvements in lung
function.
Inhaled hypertonic saline and Pulmozyme (dornase alfa) also improve clearance of mucus from
the lungs to support lung function and have been available to people with CF for many years.
Both therapies are considered to be relatively burdensome and it is not known whether either
therapy can improve or maintain lung function above what is already gained through Trikafta
use.
The goal of the SIMPLIFY study is to get information about whether or not it is safe to stop
either inhaled hypertonic saline or Pulmozyme (dornase alfa) by testing if there is a change
in lung function in subjects with cystic fibrosis (CF) who are assigned to stop their chronic
medication (either hypertonic saline or Pulmozyme) as compared to those who are assigned to
keep taking their medication while continuing to take Trikafta.
Andrew Braun, MD
All
12 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04378153
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Inclusion Criteria:
• Diagnosis of CF.
• Age ≥ 12 years at the Screening Visit.
• Forced expiratory volume in 1 second (FEV1) ≥ 70 % predicted at the Screening Visit if
< 18 years old, and ≥ 60 % predicted at Screening Visit if ≥ 18 years old.
• Clinically stable with no significant changes in health status within the 7 days prior
to and including the Screening Visit.
• Current treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for at least the 90 days
prior to and including the Screening Visit and willing to continue daily use for the
duration of the study.
• Currently taking hypertonic saline (at least 3%) and/or dornase alfa for at least the
90 days prior to and including the Screening Visit and willing to continue daily use
for the 2-week screening period.
Exclusion Criteria:
• Active smoking or vaping.
• Use of an investigational drug within 28 days prior to and including the Screening
Visit.
• Changes to chronic therapy (e.g., ibuprofen, azithromycin, inhaled tobramycin,
aztreonam lysine) within 28 days prior to and including the Screening Visit. This
includes new airway clearance routines.
• Acute use of antibiotics (oral, inhaled or IV) or acute use of systemic
corticosteroids for respiratory tract symptoms within 7 days prior to and including
the Screening Visit.
• Chronic use of systemic corticosteroids at a dose equivalent to ≥ 10mg per day of
prednisone within 28 days prior to and including the Screening Visit.
• Antibiotic treatment for nontuberculous mycobacteria (NTM) within 28 days prior to and
including the Screening Visit.
Study to Evaluate Biological & Clinical Effects of Significantly Corrected CFTR Function in Infants & Young Children (BEGIN)
This is a two-part, multi-center, prospective longitudinal, exploratory study of highly
effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators and their
impact on children with cystic fibrosis (CF).
Michael Rock, MD
All
up to 5 Years old
NA
This study is NOT accepting healthy volunteers
NCT04509050
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Inclusion Criteria:
• Part A:
• Less than 5 years of age at the first study visit.
• Documentation of a CF diagnosis.
Part B:
• Participated in Part A OR less than 6 years of age at the first study visit.
• Documentation of a CF diagnosis.
• CFTR mutations consistent with FDA labeled indication of highly effective modulator
therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor).
• Physician intent to prescribe ivacaftor or elexacaftor/tezacaftor/ivacaftor.
Exclusion Criteria:
• Part A and Part B:
Use of an investigational drug within 28 days prior to and including the first study visit.
Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 180 days prior to and
including the first study visit.
Use of chronic oral corticosteroids within the 28 days prior to and including the first
study visit.
Long-term Safety of Lumacaftor/Ivacaftor in Subjects With Cystic Fibrosis Who Are Homozygous for F508del and 12 to <24 Months of Age at Treatment Initiation
This is a Phase 3, multicenter, open-label and roll-over study in subjects who are 12 to <24
months of age at initiation of Lumacaftor/Ivacaftor (LUM/IVA) treatment.
Michael Rock, MD
All
12 Months and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04235140
Show full eligibility criteria
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Key
Inclusion Criteria:
• Subjects From Study VX16-809-122 Part B (Study 122)
• Completed the 24-week Treatment Period and the Safety Follow-up Visit in Study
122B
• Subjects Not From Study 122
• Subjects will be 1 to less than 2 years of age
• Homozygous for the F508del mutation (F/F)
Key
Exclusion Criteria:
• Any clinically significant laboratory abnormalities that would interfere with the
study assessments or pose an undue risk for the subject
• Solid organ or hematological transplantation
Other protocol defined Inclusion/Exclusion criteria may apply.
The primary purpose of this study is to discover new disease genes for rare Mendelian
disorders and its secondary purpose include diagnosing people with rare genetic disorders
that have not been previously diagnosed through conventional clinical means, learning more
about the pathobiology of genetic disorders, and developing novel diagnostic technologies and
analytics. 500 participants with undiagnosed and suspected genetic disorders will be
recruited over approximately 5 years time.
Stephen Meyn, MD, PhD
All
up to 100 Years old
NA
This study is NOT accepting healthy volunteers
NCT04586075
Show full eligibility criteria
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Inclusion Criteria:
• The applicant has a condition that remains undiagnosed despite thorough evaluation by
healthcare providers (including clinical genetic testing).
• The applicant has at least one objective finding that is likely to have an
identifiable genetic etiology.
• The applicant likely has a currently undescribed/new genetic condition or a known
genetic condition associated with a novel gene.
• The applicant/legal guardian agrees to the collection, storage and recurrent sharing
of coded information and biomaterials for research and diagnostic purposes both within
and outside of the University of Wisconsin-Undiagnosed Diseases Program (UW-UDP)
• The applicant/legal guardian agrees to receive secondary findings from genetic
testing.
• The applicant/legal guardian has sufficient proficiency in English to understand the
consent.
Exclusion Criteria:
• The applicant already has a diagnosis that explains the objective findings.
• A specific diagnosis is suspected and a standard clinical workup performed by the
referring/primary care provider would be appropriate.
• The UW-UDP is unlikely to improve on the comprehensive workup the applicant has
already received.
• The applicant's symptoms are likely multifactorial or due to a non-genetic cause.
Rare Diseases, Genetic Disease, Undiagnosed Disease, Other specified congenital malformation syndromes affecting multiple systems
Inotuzumab Ozogamicin and Blinatumomab in Treating Patients With Newly Diagnosed, Recurrent, or Refractory CD22-Positive B-Lineage Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin and blinatumomab work in treating
patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed,
has come back, or does not respond to treatment. Immunotherapy with monoclonal antibodies,
such as inotuzumab ozogamicin and blinatumomab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread.
Ryan Mattison, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT03739814
Show full eligibility criteria
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Inclusion Criteria:
• Pre-registration Eligibility Criteria (Step 0)
• Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory
prior to registration; the bone marrow sample should be from the first aspiration
(i.e. first pull). Aspirate needle should be redirected if needed to get first pull
bone marrow aspirate. It should be initiated as soon as possible after
pre-registration. The specimens should be sent to the HEME Biobank.
• Lumbar Puncture (Spinal Tap) and Intrathecal Methotrexate:
• Patients may receive the day 1 of course IA dose of intrathecal (IT)
methotrexate during the prior-to-registration lumbar puncture (or the venous
line placement) to avoid a second lumbar puncture. If the dose is
administered prior to registration, then systemic chemotherapy must begin
within 7 days of this IT chemotherapy.
• Registration Eligibility Criteria (Step 1)
• Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on
World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are
not eligible.
• CD22-positive disease defined as CD22 expression by >= 20% of lymphoblasts by local
hematopathology evaluation.
• Philadelphia chromosome/BCR-ABL1-negative ALL by cytogenetics, fluorescence in situ
hybridization (FISH), and/or polymerase chain reaction (PCR). If any test is positive
for Philadelphia chromosome/BCR-ABL1, then the patient is ineligible.
• No active central nervous system (CNS) leukemia (i.e. only CNS-1 disease allowed).
Active CNS leukemia is defined as morphologic evidence of lymphoblasts in the
cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease
within 28 days prior to registration, symptomatic CNS leukemia (i.e. cranial nerve
palsies or other significant neurological dysfunction) within the 28 days prior to
registration, and/or known asymptomatic parenchymal CNS mass lesions; see below for
additional guidance. Prophylactic intrathecal medication alone is not an exclusion.
• Categories of CNS Involvement for CNS Evaluation Prior to Registration:
• CNS 1: CSF has < 5 WBC/uL with cytospin negative for blasts; or >= 10 red
blood cell (RBC)/uL with cytospin negative for blasts.
• CNS 2: CSF has < 5 WBC/uL with cytospin positive for blasts; or >= 10 RBC/uL
with cytospin positive for blasts; or >= 10 RBC/uL, WBC/uL >= 5 but less
than Steinherz/Bleyer algorithm with cytospin positive for blasts (see
below).
• CNS 3: CSF has >= 5 WBC/uL with cytospin positive for blasts; or >= 10
RBC/uL, >= 5 WBC/uL and positive by Steinherz/Bleyer algorithm (see below);
or clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye
involvement or hypothalamic syndrome). Steinherz/Bleyer Method of Evaluating
Initial Traumatic Lumbar Punctures:
• If the patient has leukemia cells in the peripheral blood and the
lumbar puncture is traumatic and contains >= 5 WBC/uL with blasts, the
following algorithm should be used to define CNS disease: CSF WBC/CSF
RBC > 2 x (Blood WBC/Blood RBC count)
• Patients with known or suspected testicular involvement by leukemia are allowed
provided that the patient receives concomitant scrotal/testicular radiotherapy.
• Unilateral or bilateral testicular enlargement should be assessed by ultrasound
or other imaging technique. Biopsy is recommended if clinical findings are
equivocal or suggestive of hydrocele or a non-leukemic mass, but further
assessments are per treating physician discretion.
• Not pregnant and not nursing.
• This study involves agents that have known genotoxic, mutagenic, and teratogenic
effects. Therefore, for women of childbearing potential only, a negative
pregnancy test done =< 7 days prior to registration is required.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
• No unstable cardiac disease such as myocardial infarction, angina pectoris,
uncontrolled heart failure, or uncontrolled cardiac arrhythmia within 6 months of
registration.
• No impaired cardiac function, defined as left ventricular ejection fraction (LVEF) <
45% or New York Heart Association (NYHA) stage III or IV congestive heart failure
(CHF).
• Patients with known human immunodeficiency virus (HIV) infection are eligible if they
have been on effective antiretroviral therapy with an undetectable viral load tested
within 6 months of registration.
• Patients with hepatitis B virus (HBV) are eligible only if they meet all the
following:
• On HBV-suppressive therapy.
• No evidence of active virus.
• No evidence of HBV-related liver damage.
• Patients with hepatitis C virus (HCV) are eligible only if they meet all the
following:
• Successfully completed complete-eradication therapy with undetectable viral load.
• No evidence of HCV-related liver damage.
• No history of clinically relevant neurologic disorder such as epilepsy, seizure,
aphasia, stroke, severe brain injury, structural brain abnormality, benign brain
tumor, dementia, Parkinson's disease, movement disorder, cerebellar disease, or other
significant CNS abnormalities.
• No prior additional malignancy (i.e. in addition to ALL) except adequately treated
basal- or squamous-cell skin cancer, in situ cervical cancer, stage I or II cancer
from which the patient is currently in complete remission, or any other cancer from
which the patient has been disease-free for >= 2 years.
• No history of clinically significant ventricular arrhythmia, unexplained non-vasovagal
syncope, or chronic bradycardic states such as sinoatrial block or higher degree of
atrioventricular block unless a permanent pacemaker has been implanted.
• No history of chronic liver disease, including cirrhosis.
• No history of sinusoidal occlusion syndrome/veno-occlusive disease of the liver.
• No uncontrolled infection or recent history (within 4 months prior to registration) of
deep tissue infections such as fasciitis or osteomyelitis.
• Total bilirubin, serum =< 1.5 x upper limit of normal (ULN)*
• Except in the event of: 1) Gilbert disease, in which case total bilirubin must be
=< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to
leukemic infiltration, in which case total bilirubin must be =< 2 x ULN.
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine, serum =< 1.5 ULN OR creatinine clearance >= 40 mL/min
• QT interval by Fridericia's correction formula (QTcF) =< 470 msec
• Cohort 1 Patients Only
• Age >= 60 years.
• No prior treatment for ALL except a single dose of intrathecal chemotherapy,
corticosteroids, hydroxyurea, and/or leukapheresis to reduce peripheral blast count
and prevent ALL complications. Allowed therapy may be administered for no more than 14
days and must be completed >= 24 hours prior to the initiation of protocol therapy.
• No plan for allogeneic or autologous hematopoietic cell transplantation (HCT).
• Cohort 2 Patients Only:
• Age >= 18 years.
• Relapsed or refractory disease in salvage 1 or 2.
• No isolated extramedullary relapse.
• Prior allogeneic HCT permitted.
• Patients with prior allogeneic HCT must have completed transplantation >= 4 months
prior to registration.
• Patients with prior allogeneic HCT must have no evidence of graft-versus-host disease
and must have completed immunosuppressive therapy >= 30 days prior to registration.
• Prior treatment with inotuzumab ozogamicin, blinatumomab, other CD22-directed therapy,
or other CD19-directed therapy is not allowed.
• Prior treatment with rituximab must be completed >= 7 days prior to registration.
• Prior treatment with other monoclonal antibodies must be completed >= 6 weeks prior to
registration.
• Prior treatment for ALL must be completed >= 14 days prior to registration with the
following exceptions: intrathecal chemotherapy, hydroxyurea, corticosteroids,
6-mercaptopurine, methotrexate, vincristine, and/or leukapheresis to reduce
circulating absolute lymphoblast count to =< 10,000/uL or prevent complications
related to ALL are allowed but must be completed >= 24 hours prior to the initiation
of protocol therapy.
• Patients should have resolution of any acute non-hematologic toxicities of prior
therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events (CTCAE) version (v)5.0 grade =< 1.
• Peripheral blood absolute lymphoblast count =< 10,000/uL (treatment allowed as above
to reduce blast count to =< 10,000/uL)
Lymphoid Leukemia, Leukemia, B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia
Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations
This BVD-523-ABC study builds on the safety and clinical activity experience of previous
studies that have evaluated ulixertinib as a novel targeted cancer treatment in cohorts of
patients with specific genetic alterations and tumor histologies that result in aberrant MAPK
pathway signaling. Early clinical data have demonstrated anti-tumor activity with ulixertinib
treatment and have identified specific groups of patients for whom additional development is
warranted.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04488003
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Inclusion Criteria:
• Patients with a locally advanced or metastatic malignancy, that has progressed
following systemic therapy for their disease, if available, or for which the patient
is not a candidate or refuses.
• Tumors harboring a MEK or atypical BRAF alteration.
• Provide signed and dated informed consent prior to initiation of any study-related
procedures that are not considered standard of care (SoC).
• Male or female patients aged ≥18 years.
• Patients must have measurable disease by RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 •2.
• Adequate renal function [creatinine ≤1.5 times ULN (upper limit of normal)] or a
glomerular filtration rate (GFR) of ≥50 mL/min (using Cockcroft-Gault).
• Adequate hepatic function [total bilirubin ≤1.5 times ULN; AST (aspartate
transaminase) and ALT (alanine transaminase) ≤3 times ULN or ≤5 times ULN if the
elevation is due to liver involvement by tumor].
• Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x 109 cells/L;
absolute neutrophil count ≥1.5 x 109 cells/L).
• Adequate cardiac function: Left ventricular ejection fraction (LVEF) of >50% as
assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); and
a corrected QT interval (QTc) <480ms by the Fridericia method (QTcF).
• Contraception •women: Negative pregnancy test for females of child-bearing potential;
must be surgically sterile, postmenopausal (no menstrual cycle for at least 12
consecutive months), or compliant with a medically approved contraceptive regimen
during and for 3 months after the last administration of study drug. Abstinence is not
considered an adequate contraceptive regimen.
• Contraception •men: Must be surgically sterile, or compliant with a medically
approved contraceptive regimen during and for 3 months after the last administration
of study drug.
• Willing and able to participate in the trial and comply with all trial requirements.
• Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational agent may be included after consultation with the medical monitor.
Exclusion Criteria:
• Gastrointestinal (GI) condition that could impair absorption of study medication
(specific cases e.g., remote history of GI surgery, may be enrolled after discussion
with the medical monitor) or inability to ingest study medication.
• Uncontrolled or severe intercurrent medical condition.
• Known uncontrolled brain metastases. Stable brain metastases either treated or being
treated with a stable dose of steroids/anticonvulsants, with no dose change in the
previous 4 weeks, can be allowed.
• Having received any cancer-directed therapy (chemotherapy, hormonal therapy, biologic
or immunotherapy, etc.) within 28 days or 5 half-lives (whichever is shorter) prior to
the first dose of study drug. Patients previously treated with radiotherapy must have
recovered from the acute toxicities associated with such treatment.
• Major surgery within 4 weeks prior to first dose.
• Any use of an investigational drug within 28 days or 5 half-lives (whichever is
shorter) prior to the first dose of study drug. A minimum of 10 days between
termination of the prior investigational drug and administration of study drug is
required. In addition, any drug-related toxicity except alopecia should have recovered
to Grade 1 or less.
• Prior therapy with any ERK inhibitor (e.g. LY3214996, LTT462).
• Groups 1-4: Prior therapy with any BRAF and/or MEK inhibitor (e.g. encorafenib,
dabrafenib, vemurafenib, binimetinib, trametinib, cobimetinib) is excluded. Prior BRAF
and/or MEK inhibitor therapy is permitted for Groups 5 and 6.
• For Part B, agents targeting BRAF or MEK kinases and experimental agents are not
permitted as physician's choice
• Pregnant or breast-feeding women.
• Any evidence of serious active infections. Patients are allowed to enroll if they have
been fever-free for at least 48 hours and are on an active treatment that is not
prohibited in Appendix 1 of the protocol.
• Any important medical illness or abnormal laboratory finding that would increase the
risk of participating in this study (based on the investigator's judgment).
• A history or current evidence/risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR).
• Concurrent therapy with any other investigational agent.
• Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2,
CYP2D6, and CYP3A4.
Advanced Solid Tumor, BRAF Gene Mutation, BRAF Gene Alteration, MEK Mutation, MEK Alteration, MAP2K1 Gene Mutation, MAP2K1 Gene Alteration, MAP2K2 Gene Mutation, MAP2K2 Gene Alteration, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Prospective Study of Pregnancy in Women With Cystic Fibrosis (MAYFLOWERS)
In this study, the investigators aim to evaluate changes in lung function in women with
cystic fibrosis (CF) during pregnancy and for 2 years after pregnancy based on exposure to
highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
Erin Lowery, MD
Female
16 Years and over
NA
This study is NOT accepting healthy volunteers
NCT04828382
Show full eligibility criteria
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Inclusion Criteria:
• Pregnant, intending to continue pregnancy, enrolled in the CFF registry
Ph 1/2 Study Evaluating Safety and Tolerability of Inhaled AP-PA02 in Subjects With Chronic Pseudomonas Aeruginosa Lung Infections and Cystic Fibrosis (SWARM-Pa)
Phase 1b/2a, double-blind, randomized, placebo-controlled, single and multiple ascending dose
study to evaluate the safety, tolerability and phage recovery profile of AP-PA02
multi-bacteriophage therapeutic candidate administered by inhalation in subjects with cystic
fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection.
Andrew Braun, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04596319
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Key
Inclusion Criteria:
• ≥ 18 years old
• Body mass index (BMI) of ≥ 18 kg/m2
• Documented diagnosis of CF
• Evidence of chronic pulmonary Pseudomonas aeruginosa infection
• Willing to undergo sputum induction procedures at designated study visits, and willing
to provide expectorated sputum samples at all other timepoints (for subjects who are
able to expectorate)
• FEV1 ≥ 60% of predicted normal [per Global Lung Function Initiative (GLI) standards]
at Screening
• Adequate renal function
Key
Exclusion Criteria:
• Recent significant weight loss
• Abnormal vital signs at Screening
• History of prolonged QT syndrome
• Use of supplemental oxygen during the day at rest
• Abnormal liver function tests greater than 3X the upper limit of normal (ULN)
• Recent oral or IV antibiotics received for acute pulmonary exacerbation. Inhaled
antibiotic use for chronic suppression of P. aeruginosa is acceptable.
• Recent clinically significant infection requiring systemic antimicrobial therapy
• Currently receiving anti-pseudomonal antibiotic treatment for acute sinusitis.
• Currently receiving systemic corticosteroids
• Currently receiving treatment for active infection with nontuberculous mycobacteria
(NTM), Staphylococcus aureus, or Burkholderia cepacia complex lung infection
• Currently receiving treatment for aspergillosis or ABPA (allergic bronchopulmonary
aspergillosis)
• Initiation of a CFTR potentiator/corrector therapy, such as Trikafta®, less than 90
days prior to Screening
• Acquired or primary immunodeficiency syndromes
• Active pulmonary malignancy (primary or metastatic)
• History of lung transplantation
• Recent hemoptysis
• Female pregnant or breastfeeding
• Heavy smoker
A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)
The purpose of this study is to evaluate the efficacy and safety of
VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are heterozygous
for F508del and a minimal function mutation (F/MF participants).
Andrew Braun, MD
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05033080
Show full eligibility criteria
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Key
Inclusion Criteria:
• Heterozygous for F508del and a minimal function mutation (F/MF genotype)
• Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean
for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy;
FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA
Key
Exclusion Criteria:
• History of solid organ or hematological transplantation
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh
Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• Pregnant or breast-feeding females
Other protocol defined Inclusion/Exclusion criteria may apply
A Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Who Are Homozygous for F508del, Heterozygous for F508del and a Gating (F/G) or Residual Function (F/RF) Mutation, or Have At Least 1 Other Triple Combination Responsive (TCR) CFTR Mutation and No F508del Mutation
The purpose of this study is to evaluate the efficacy and safety of
VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are homozygous for
F508del, heterozygous for F508del and a gating (F/G) or residual function (F/RF) mutation, or
have at least 1 other TCR CF transmembrane conductance regulator (CFTR) gene mutation and no
F508del mutation.
Andrew Braun, MD
All
12 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05076149
Show full eligibility criteria
Hide eligibility criteria
Key
Inclusion Criteria:
• Participant has one of the following genotypes:
• Homozygous for F508del;
• Heterozygous for F508del and a gating (F/G) mutation;
• Heterozygous for F508del and a residual function (F/RF) mutation;
• At least 1 other TCR CFTR gene mutation identified as responsive to ELX/TEZ/IVA
and no F508del mutation
• Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean
for age, sex, and height for participants currently receiving CFTR protein modulator
therapy; FEV1 >=40% and <=80% for participants not currently receiving CFTR protein
modulator therapy
Key
Exclusion Criteria:
• History of solid organ or hematological transplantation
• Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh
Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15)
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• Pregnant or breast-feeding females
Other protocol defined Inclusion/Exclusion criteria may apply
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