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Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA)

Phase 1
Open (Enrolling)
Fanconi Anemia

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Trial Information

Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA)


I. To determine the safety of lentiviral gene transfer for patients with Fanconi anemia
complementation group A (FANCA).


I. To determine the feasibility of collection of the number of hematopoietic progenitor
cells from Fanconi anemia complementation group A patients that would be expected to have
potential for therapeutic benefit after transduction and infusion. The mobilization will be
performed with G-CSF (filgrastim) or with a combination of G-CSF and plerixafor for patients
aged 18 and older. Additional bone marrow may be collected if insufficient cells are
collected after mobilization and apheresis.

II. To determine the transduction efficiency for human FA patient hematopoietic progenitor
cells transduced with a clinical grade lentiviral vector encoding the gene for Fanconi
anemia complementation group A.

III. To determine if the clinical grade transduction will result in phenotypic correction of
gene modified cells by in vitro assays.

IV. To determine if infusion of FANCA gene-modified cells will result in engraftment and
improvement in blood counts in FA patients.


STEM CELL MOBILIZATION: Patients receive filgrastim subcutaneously (SC) twice daily on days
-5 to -1. Patients 18 years of age or older also receive plerixafor SC on days -2 and -1.

CELL COLLECTION: Patients undergo apheresis for collection of stem/progenitor cells on days
-2 and -1. Patients with insufficient cell mobilization (< 1 x 10^6 CD34+ cells/kg) undergo
bone marrow harvest.

REINFUSION: Patients undergo reinfusion of genetically modified hematopoietic progenitor
cells on day 0.

After completion of study treatment, patients are followed up periodically for 15 years.

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, or acquisition of mitomycin C resistance
after in vitro lentiviral transduction with a vector bearing the cDNA for Fanconi
complementation group A

- 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 =< 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%

- 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 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

- 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 Heart Association [NYHA]
II), poorly controlled diabetes (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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity and safety of lentiviral gene transfer

Outcome Description:

Adverse events will be graded by Common Terminology Criteria for Adverse Events (CTCAE), Version 4.

Outcome Time Frame:

Up to 15 years

Safety Issue:


Principal Investigator

Pamela Becker

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

February 2012

Completion Date:

Related Keywords:

  • Fanconi Anemia
  • Anemia
  • Fanconi Anemia
  • Fanconi Syndrome



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109