Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
Status:
Terminated
Trial end date:
2009-09-01
Target enrollment:
Participant gender:
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
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