Allogeneic SCT Of Pts With SCID And Other Primary Immunodeficiency Disorders
Status:
Terminated
Trial end date:
2009-10-01
Target enrollment:
Participant gender:
Summary
This study is to discover whether children with severe combined immunodeficiency disease
(SCID) or other primary immunodeficiency disorder (PID) for which no satisfactory treatment
other than stem cell transplantation (SCT) exists can be safely and effectively transplanted
from HLA mismatched (up to one haplotype) related donors or unrelated matched or mismatched
(up to one antigen) donors, when leukocytolytic monoclonal antibodies (MAb) and Fludarabine
are the sole conditioning agents. Three monoclonal antibodies will be used in combination.
Two of them are rat IgG1 (immunoglobulin G1) 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. Campath 1H, Alemtuzumab, has been licensed
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 SCID, in whom the use of conventional chemotherapeutic agents for
conditioning may produce or aggravate unacceptable and even lethal short 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 GvHD prophylaxis. Additional Graft versus Host Disease
(GvHD) prophylaxis may be provided by administration of 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