Gene Therapy for Fanconi Anemia

• Register: ClinicalTrials.gov
• Last refreshed on: 25 July 2023
• Main ID: NCT01331018
• Date of registration: 16/03/2011
• Prospective Registration: Yes
• Primary sponsor: Fred Hutchinson Cancer Center
• Public title: Gene Therapy for Fanconi Anemia
• Scientific title: Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA)
• Date of first enrolment: February 22, 2012
• Target sample size: 3
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01331018
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Hans-Peter Kiem
• Affiliation: Fred Hutch/University of Washington Cancer Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- FA demonstrated by a positive test for increased sensitivity to chromosomal breakage
with mitomycin C or diepoxybutane performed by a Clinical Laboratory Improvement
Amendments (CLIA) or College of American Pathologists (CAP) approved laboratory

- FA complementation group A as determined by somatic cell hybrids, molecular
characterization, western blot analysis, acquisition of mitomycin C resistance after
in vitro lentiviral transduction with a vector bearing the complementary
deoxyribonucleic acid (cDNA) for Fanconi complementation group A, or other clinically
certified method of complementation group analysis

- Bone marrow analysis demonstrating normal cytogenetics, and no more than 5% of cells
with a single clonal abnormality by fluorescence in situ hybridization (FISH) for
myelodysplastic syndrome (MDS) panel within 3 months of stem cell collection

- Signed informed consent by the patient or legally authorized representative

- Absolute neutrophil count >= 0.5 x 10^9/L

- Hemoglobin >= 8 g/dL

- Platelet count >= 20 x 10^9/L and able to achieve a platelet count of >= 50 x 10^9/L
with transfusion support

- Adequate hepatic function with aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 5 x upper limit of normal (ULN)

- Adequate renal function with creatinine (Cre) =< 1.5; if greater, then glomerular
filtration rate (GFR) > 60 mL/min/1.73 m^2 as calculated by the Modification of Diet
in Renal Disease equation

- Adequate pulmonary function with corrected diffusion capacity of carbon monoxide
(DLCO) > 50% in those for whom this study can be performed

- For subjects < 17 years of age, Modified Lansky Play-Performance Score of >= 70%; for
subjects 17 and older, Karnofsky score of >= 70%

Exclusion Criteria:

- Non-hematopoietic malignancy where the expected survival is less than 2 years

- Myelodysplastic syndrome as defined by World Health Organization (WHO) criteria

- Acute myeloid leukemia as defined by WHO criteria

- Pregnancy or lactation; females of childbearing potential and males who are admitted
to the study will be advised that the study procedures and study drugs may be
teratogenic, and they will be required to take adequate measures to prevent conception
for the duration of the study

- Concurrent enrollment in any other study using an investigational drug

- Physical or emotional status that would prevent informed consent, protocol compliance,
or adequate follow-up

- Patients for whom an human leukocyte antigen (HLA) matched sibling donor bone marrow
transplant is being actively pursued will not be eligible for study until it is
determined that no sibling donor is available or that a stem cell transplant is not
feasible during the time the patient might be on study

- No patient will be included in this study as an alternative to a clinically
indicated HLA matched sibling donor stem cell transplant

- If an HLA matched sibling donor is identified, but stem cell or marrow collection
is not feasible (e.g., donor is in utero, is a newborn from whom cord blood was
not collected, or is unable to undergo a donation procedure because of ill
health), a patient may be included in the study at the discretion of the
investigators

- Significant associated diseases including documented human immunodeficiency virus
(HIV) infection, uncontrolled hypertension (diastolic blood pressures > 95%ile for
age), unstable angina, congestive heart failure (> New York [NY] class II), poorly
controlled diabetes (hemoglobin A1c [Hgb A1c] > 7%), coronary angioplasty within 6
months, myocardial infarction within the last 6 months, or uncontrolled atrial or
ventricular cardiac arrhythmia, abnormal coagulation, persistent abnormal urinalysis
reflecting intrinsic renal disease

- Active ongoing viral, bacterial, or fungal infection



Age minimum: 4 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Fanconi Anemia

Intervention(s)

Drug: Methylprednisolone

Procedure: Bone Marrow Aspiration

Other: Laboratory Biomarker Analysis

Biological: Filgrastim

Procedure: Leukapheresis

Biological: Genetically Engineered Hematopoietic Stem Progenitor Cells

Drug: Plerixafor

Drug: Prednisone

Primary Outcome(s)

Development of replication competent lentivirus [Time Frame: Up to 15 years]

Development of insertional mutagenesis or hematologic malignancy [Time Frame: Up to 15 years]

Toxicity of gene transfer [Time Frame: Up to 15 years]

Hematological and non-hematological organ toxicity [Time Frame: Up to 15 years]

Secondary Outcome(s)

Demonstrable functional expression by growth of recipient cells in mitomycin C [Time Frame: 3 months]

Efficacy of G-CSF and plerixafor mobilization in Fanconi anemia (FA) patients [Time Frame: Up to 6 days]

Transduction efficiency [Time Frame: Day 0]

Improved blood counts [Time Frame: Up to 15 years]

Detectable levels of transduced cells in blood and marrow [Time Frame: Up to 1 year]

Efficacy of lineage depletion of bone marrow or mobilized cell product [Time Frame: Up to 15 years]

Secondary ID(s)

2097.00

NCI-2011-00202

RG9212015

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Rocket Pharma Limited

National Heart, Lung, and Blood Institute (NHLBI)