Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia

NCT00272857 | Completed Phase 1 DMC

• 4 other identifiers: 382R01HL081499CCHMCEH002R01HL081499-01A1
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Fanconi anemia (FA) is a disease that affects an individual's bone marrow. It is caused by a defective gene in the bone marrow cells that produce various types of blood cells. Individuals with FA may experience fatigue, bleeding, and increased infections. The purpose of this study is to evaluate the safety and effectiveness of a gene transfer procedure in generating new, healthy cells in individuals with FA.

Conditions

Fanconi Anemia

Outcome Measures

Primary Outcomes (2)

• Safety of gene transfer methods

  3months, 6 months and yearly up to 15 years post gene transfer

• Short-term and long-term engraftment of gene-corrected autologous hematopoietic cells (all measured at Year 1)

  3months, 6 months and yearly up to 15 years post gene transfer

Secondary Outcomes (4)

• Frequency and function of the integrated recombinant Fanconi vector

  3months, 6 months and yearly up to 15 years post gene transfer

• Efficiency of engraftment of multilineage gene corrected clones

  3months, 6 months and yearly up to 15 years post gene transfer

• Lineage contribution and longevity of molecularly distinguishable gene marked clones

  3months, 6 months and yearly up to 15 years post gene transfer

• Development of myelodysplastic syndrome or overt leukemia (all measured at Year 1)

  3months, 6 months and yearly up to 15 years post gene transfer

Study Arms (1)

Single arm

EXPERIMENTAL

Genetic: Retrovirus Construct

Interventions

Retrovirus Construct GENETIC

This study will use an experimental gene transfer procedure performed in a laboratory to insert a new FA gene into the participant's bone marrow cells. The gene-corrected bone marrow cells will then be re-infused into the participant and participants will be observed for successful gene transfer

Single arm

Eligibility Criteria

• Age: 1 Year - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• FA, as determined by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane
• FA complementation group A, as determined by somatic cell hybrids or molecular characterization; transduction of peripheral blood or bone marrow cells with the complementation group of specific retrovirus used in this study must demonstrate correction of mitomycin C sensitivity or cell cycle arrest
• Weighs at least 7.5 kg
• Normal cytogenetics on bone marrow within 3 months of study entry
• A minimum of 2 x 10(6) CD34+ cells/kg after CD34+ selection of the harvested bone marrow or mobilized peripheral blood product must be available to proceed with thaw (if cryopreserved) and transduction
• Human leukocyte antigen (HLA) typing with initial donor limited search results that indicate a potentially acceptable matched unrelated donor in the National Marrow Donor Program database

You may not qualify if:

• Cancer
• Clonal cytogenetic abnormality on bone marrow or peripheral blood karyotype within 3 months of study entry
• Myelodysplastic syndrome based on the FAB classification including:
• Refractory anemia with ringed sideroblasts (RARS)
• Refractory anemia with excess blasts (RAEB)
• RAEB in transformation (RAEB-T)
• Chronic myelomonocytic leukemia (CMML) (myelodysplastic changes in greater than two cell lines, refractory anemia alone, or aplastic anemia with dysplastic changes are permitted)
• Positive baseline screening result for both of the following:
• Detection of Fanconi A proviral sequences by polymerase chain reaction (PCR) analysis
• Detection of replication competent retrovirus by repeat testing by PCR of gibbon ape leukemia virus (GALV) envelope sequence or a positive S+L- assay
• Pregnant or breastfeeding; women of childbearing potential who are enrolled will be advised that the drug may cause birth defects and will be required to use an acceptable form of contraception
• Concurrent enrollment in any other study using an investigational agent, excluding androgens and thyroxine
• Physical or emotional status that would prevent informed consent, protocol compliance, or adequate follow-up with participant or legal guardian
• Participants for whom an acceptable HLA identical matched sibling donor (HLA A, B, DRB1; 6/6 match) has been identified (HLA typing of normal siblings must be documented)

Sponsors & Collaborators

• Boston Children's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• Kelly PF, Radtke S, von Kalle C, Balcik B, Bohn K, Mueller R, Schuesler T, Haren M, Reeves L, Cancelas JA, Leemhuis T, Harris R, Auerbach AD, Smith FO, Davies SM, Williams DA. Stem cell collection and gene transfer in Fanconi anemia. Mol Ther. 2007 Jan;15(1):211-9. doi: 10.1038/sj.mt.6300033.

  PMID: 17164793 BACKGROUND

MeSH Terms

Conditions

Fanconi Anemia

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Franklin O. Smith, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: January 4, 2006
• First Posted: January 9, 2006
• Study Start: August 1, 2004
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: June 23, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)