NCT01036009

A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 6 Months – 25 Years
• Healthy volunteers: Not accepted

Summary

There is no curative therapy once acute leukemia patients relapse after transplant. Patients who develop clinically significant graft versus host disease (GVHD) have a lower rate of relapse than those who do not develop GVHD. We are initiating this study of post-transplant fast withdrawal of immunosuppression and donor lymphocyte infusions, with a goal of achieving full donor chimerism in children with hematologic malignancies. If our hypothesis that full donor chimerism results in leukemia-free survival is correct, using immune modulation to achieve full donor chimerism should decrease relapse rate and thus increase survival. The goal of this Phase II study is to identify if achieving full donor chimerism in whole blood CD3+ and leukemia-specific (CD14/15+, CD19+, CD33+ and CD34+) subset may decrease the risk of relapse of patients undergoing allogeneic transplant for hematologic malignancy.

Detailed description

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 hematologic malignancy. 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.

Conditions

• Acute Leukemia
• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Biphenotypic Leukemia
• Pre-leukemic Syndromes
• Monosomy 7
• Bone Marrow Clonal Malformations
• Juvenile Myelomonocytic Leukemia
• Myelodysplastic Syndromes
• Chronic Myelogenous Leukemia

Interventions

Type	Name	Description
OTHER	Withdrawal of immunosuppression and donor lymphocyte infusion	Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.

Timeline

• Start date: 2009-10-01
• Primary completion: 2014-07-01
• Completion: 2015-07-01
• First posted: 2009-12-21
• Last updated: 2016-06-23
• Results posted: 2014-10-31

Locations

2 sites across 1 country: United States