Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia

Plain-language summary

This study examines a gene therapy that aims to transfer a healthy gene into bone marrow cells via a retrovirus in individuals with Fanconi anemia. It enrolled individuals with complementation group A Fanconi anemia who had normal bone marrow cytogenetics. The research was conducted in Phase 1 and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

Boston Children's Hospital

Intervention

Retrovirus Construct

Start date

8/1/2004

Estimated completion

10/1/2007

Countries

United States

Related genes

Locations

• Cincinnati, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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:

  1. Refractory anemia with ringed sideroblasts (RARS)
  2. Refractory anemia with excess blasts (RAEB)
  3. RAEB in transformation (RAEB-T)
  4. 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:

  1. Detection of Fanconi A proviral sequences by polymerase chain reaction (PCR) analysis
  2. 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)