Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
Stopped: drug company is no longer making the drug
United States3 participantsStarted 2010-09
Plain-language summary
Allogeneic blood and marrow transplantation remains the only viable cure for children who suffer from many serious non-malignant hematological diseases. Transplantation, however, carries a high risk of fatal complications. Much of the risk stems from the use of high dose radiation and chemotherapy for conditioning, the treatment administered just prior to transplant that eliminates the patients' marrow and immune system, effectively preventing rejection of the donors' cells. Attempts to make blood and marrow transplantation safer for children with non-malignant diseases by using lower doses of radiation and chemotherapy have largely failed because of a high rate of graft rejection.
In many such cases, it is likely that the graft is rejected because the recipient is sensitized to proteins on donor cells, including bone marrow cells, by blood transfusions. The formation of memory immune cells is a hallmark of sensitization, and these memory cells are relatively insensitive to chemotherapy and radiation. Alefacept, a drug used to treat psoriasis, on the other hand, selectively depletes these cells. The investigators are conducting a pilot study to begin to determine whether incorporating alefacept into a low dose conditioning regimen can effectively mitigate sensitization and, thereby, prevent rejection of allogeneic blood and marrow transplants for multiply transfused children with non-malignant hematological diseases.
Who can participate
Age range21 Years
SexALL
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Inclusion criteria
✓. Must be between the ages of 0-21 years at the time of admission for transplant
✓. Must have been transfused with at least five platelet, erythrocyte or granulocyte units (partial or full)
✓. Must have one of the following diseases:
✓. Must have an available HLA identical sibling (HLA matched related), a non-HLA identical parent or sibling who is matched at least seven of eight loci (mismatch can be at an allele or antigen level), an unrelated adult donor who is matched at least seven of eight loci (mismatch can be at an allele or antigen level) or an unrelated cord blood unit that is matched at five of six loci (A (antigen level), B (antigen level), DRB1 (allele level)) and provides a minimum pre-cryopreservation TNC dose of 5.0 x 107 TNC/kg recipient weight.
Exclusion criteria
✕. Hemophagocytic lymphohistiocytosis or other disorder characterized by NK cell dysfunction, since alefacept's effect is mediated by NK cells.
✕. Biopsy proven cirrhosis (score IV).
✕. SCD chronic lung disease ≥ stage III (see appendix 1)
What they're measuring
1
Feasibility of Alefacept Pre-conditioning, Measured by Number of Subjects With Full Donor Engraftment
. Severe renal dysfunction defined as estimated GFR of \<30 ml/min.
✕. Severe cardiac dysfunction defined as shortening fraction \< 25%.
✕. Severe neurologic impairment other than hemiplegia alone, defined as full scale IQ ≤ 70, quadriplegia or paraplegia, inability to ambulate, inability to communicate without assistive device, or any impairment resulting in decline of Lansky performance score to \<50%.
✕. Karnofsky or Lansky functional performance score \< 50%