Overview

Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia

Status:
Terminated
Trial end date:
2009-09-01
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this study is to discover whether children and adults with Fanconi anemia (FA) can be safely and effectively transplanted with Human Leukocyte Antigen (HLA) mismatched (up to one haplotype), HLA-matched sibling, or unrelated donor stem cells, when leukocytolytic monoclonal antibodies are the sole conditioning agents (patients receiving an HLA mismatched transplant will receive Fludarabine as part of the conditioning regimen). Three monoclonal antibodies (MAb) will be used in combination. Two of them, YTH 24 and YTH 54 are rat antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of >90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. This MAb has been widely used to treat B cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with Fanconi anemia, in whom the use of conventional chemotherapeutic agents for conditioning produces a high rate of short and long term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial graft versus host disease (GvHD) prophylaxis. Additional GvHD prophylaxis will be provided by administration of the medication FK506.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Baylor College of Medicine
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital Research Institute
The Methodist Hospital System
Treatments:
Alemtuzumab
Antibodies
Fludarabine
Fludarabine phosphate
Criteria
Inclusion Criteria:

Diagnosis of Fanconi Anemia or other suspected DNA breakage/chromosomal instability
syndromes, such as dyskeratosis congenita or Nijmegen breakage syndrome of all ages are
eligible.

Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow
sensitivity to mitomycin C or DEB or clinical evidence of other DNA breakage/chromosomal
instability syndrome as determined by genetic testing or clinical diagnosis by a geneticist

Severe aplasia anemia as evidenced by a hypocellular bone marrow and at least 1 of the 3
criteria below: ANC < 500/mm3 Hemoglobin < 10 gm/dl with reticulocyte count < 1% Platelet
count < 50,000/mm3

Availability of an HLA matched or mismatched (up to one haplotype) family member who has
been documented not to have Fanconi anemia or of an unrelated HLA matched stem cell donor.
Fully matched is defined at 6/6 match by high resolution DR based DNA typing.

Life expectancy greater than 6 weeks limited by diseases other than FA

Creatinine 2X normal for age or less

Karnofsky score 70% or more

Exclusion Criteria:

Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by
echocardiogram (i.e., shortening fraction less than 25%).

Patients with known allergy to rat serum products.

Patients with a severe infection that on evaluation by the Principal Investigator precludes
ablative chemotherapy or successful transplantation.

Patients with severe personality disorder or mental illness.

Patients with documented HIV positivity.

Pregnant

NOTE: Patients who would be excluded from the protocol strictly for laboratory
abnormalities can be included at the investigator's discretion after approval by the CCGT
Protocol Review Committee and the FDA Reviewer.