Gene Therapy for Fanconi Anemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Fred Hutchinson Cancer Research Center
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center Identifier:
First received: March 16, 2011
Last updated: August 18, 2015
Last verified: August 2015

This pilot trial will access the toxicity and efficacy of infusion of gene modified cells for patients with Fanconi anemia (FA). Infusion of autologous patient blood stem cells that have been corrected in the laboratory by introduction of the normal gene may improve blood counts in patients with FA.

Condition Intervention Phase
Fanconi Anemia
Procedure: Harvest Procedure
Biological: Genetically Engineered Hematopoietic Stem Progenitor Cells
Other: Laboratory Biomarker Analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gene Transfer for Patients With Fanconi Anemia Complementation Group A (FANCA)

Resource links provided by NLM:

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Hematological and non-hematological organ toxicity [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    Adverse events will be graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.

  • Development of insertional mutagenesis or hematologic malignancy [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    Adverse events will be graded by CTCAE, version 4.

  • Development of replication competent lentivirus [ Time Frame: Up to 15 years ] [ Designated as safety issue: Yes ]
    Adverse events will be graded by CTCAE, version 4.

Secondary Outcome Measures:
  • Transduction efficiency [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    After completion of lentiviral transduction, the percent gene modified cells will be determined by molecular studies.

  • Detectable levels of transduced cells in blood and marrow [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Blood and bone marrow samples will be assayed by real-time quantitative polymerase chain reaction (PCR).

  • Improved blood counts [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Complete blood counts will be monitored, initially weekly, then monthly during the first year, then quarterly during the 2nd year after infusion.

  • Demonstrable functional expression by growth of recipient cells in mitomycin C [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Blood and bone marrow cells will be assayed for viability of cultured cells and hematopoietic colonies in the presence of the chemotherapy drug and deoxyribonucleic acid (DNA) crosslinking agent, mitomycin C.

Estimated Enrollment: 10
Study Start Date: February 2012
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (hematopoietic stem progenitor cells)

BONE MARROW HARVEST FOR CELL COLLECTION: Patients undergo bone marrow harvest for collection of stem/progenitor cells on day -1.

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

Procedure: Harvest Procedure
Undergo bone marrow harvest
Other Name: Harvest
Biological: Genetically Engineered Hematopoietic Stem Progenitor Cells
Undergo infusion of genetically modified hematopoietic progenitor cell therapy
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:


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


I. 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.

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

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


BONE MARROW HARVEST FOR CELL COLLECTION: Patients undergo bone marrow harvest for collection of stem/progenitor cells on day -1.

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.


Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 complementary deoxyribonucleic acid (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 (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%
  • 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 Heart Association [NYHA] 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01331018

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Pamela S. Becker    206-616-1589      
Principal Investigator: Pamela S. Becker         
Principal Investigator: Hans-Peter P. Kiem         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Principal Investigator: Pamela Becker Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center Identifier: NCT01331018     History of Changes
Other Study ID Numbers: 2097.00, NCI-2011-00202, 2097.00, P30CA015704
Study First Received: March 16, 2011
Last Updated: August 18, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fanconi Anemia
Fanconi Syndrome
Anemia, Aplastic
Anemia, Hypoplastic, Congenital
Bone Marrow Diseases
DNA Repair-Deficiency Disorders
Genetic Diseases, Inborn
Hematologic Diseases
Kidney Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Renal Tubular Transport, Inborn Errors
Urologic Diseases processed this record on August 26, 2015