A Phase II Study of Preemptive Fast Withdrawal of Immunosuppression and Donor Lymphocyte Infusions for Achieving Complete Donor Chimerism Following Allogeneic Transplant for Pediatric Hematologic Malignancies
The goal of this Phase II study is to identify if achieving full donor chimerism in whole
blood, CD3+, and leukemia-specific subset (CD3+, CD14/15+, CD19+, CD33+ and CD34+ subset)
may decrease the risk of relapse of patients undergoing allogeneic transplant for
We estimate that total of 50 recipient patients will need to be enrolled. Of these 50
recipient patients an observation group and an intervention group will be formed. We want
to enroll 25 recipient patients in the intervention group, this group will receive study
intervention and their outcomes will be the focus of statistical analysis for this study.
Intervention will involve fast withdrawal of immunosuppression following transplant and
donor lymphocyte infusion (DLI) until full donor chimerism is achieved. Chimerism is a
genetic test that measures the proportion of donor's and recipient's cells in blood or bone
marrow. Twenty five patients will undergo fast withdrawal of immunosuppression and 33 -50%
of them (8-13) will undergo DLI following fast withdrawal of immunosuppression.
Patients will have peripheral blood (PB) chimerism tested upon engraftment. A confirmatory
test from PB and bone marrow (BM) will be done on day 45±7. Minimal residual disease (MRD)
will be examined by immunoflow, FISH, cytogenetics or PCR. Patients with positive MRD will
be on a faster schedule of immune intervention than patients with negative MRD.
Interventions will be carried on until 1 year post transplant. If confirmatory testing shows
no evidence of MRD and full donor chimerism is present in all subsets, the patient will be
part of the "observation" group and be observed until 2 years post transplant. Chimerism
will be repeated at 12 and 24 months post transplant. If the patient has mixed chimerism on
both confirmatory tests (PB and BM), the patient will be part of the "intervention" group
and fast withdrawal of immunosuppression will be initiated. If the patient has mixed
chimerism on one of the confirmatory tests (PB or BM), the test will be repeated in 2 weeks
and the patient will proceed with either observation or intervention, based on the result of
the repeated test. Patients will be followed for the incidence of acute and chronic Graft
Versus Host Disease (GVHD) and relapse until 2 years post transplant. The study will be
considered successful if the relapse rate at 2 years post transplant is ≤20% for the entire
study or ≤ 40% for the intervention group.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Relapse rate at 2 years post-transplant.
2 years post transplant.
Biljana Horn, M.D.
University of California, San Francisco
United States: Institutional Review Board
|All Children's Hospital||St. Petersburg, Florida 33701|
|University of California||San Francisco, California 94108|