Overview

This trial is active, not recruiting.

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
Treatment withdrawal of immunosuppression and donor lymphocyte infusion
Phase phase 2
Sponsor University of California, San Francisco
Collaborator All Children’s Hospital Johns Hopkins Medicine
Start date October 2009
End date July 2014
Trial size 50 participants
Trial identifier NCT01036009, CC# 09082, NCT00975598

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(No Intervention)
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
(Experimental)
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
withdrawal of immunosuppression and donor lymphocyte infusion
Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.

Primary Outcomes

Measure
Relapse rate at 2 years post-transplant.
time frame: 2 years post transplant.

Secondary Outcomes

Measure
2 years post-transplant survival. The incidence of acute and chronic GVHD.
time frame: 2 years post transplant

Eligibility Criteria

Male or female participants from 6 months up to 25 years old.

Inclusion Criteria: - Age 6 months - 25 years. - Diagnoses of acute leukemia (AML, ALL, biphenotypic leukemia), pre-leukemic syndromes (monosomy 7 or other bone marrow clonal malformations), JMML, myelodysplastic syndromes or CML. - Undergoing an allogeneic transplant as standard care. - Performance status: Karnofsky/Lansky>60%. - Availability of pre-transplant recipient's DNA and donor's DNA for chimerism testing. This could be DNA or material from which DNA could be extracted. Frozen blood would be preferred. For some patients, post transplant specimens that are not infiltrated with donor cells may be used. - Bone marrow or PBMTC as stem cell source.HLA matching: donor and recipient should be matched at a minimum of 7/8 antigens (A,B,C and DrB1) for bone marrow and PBMTC transplants. - No history of ≥grade III acute GVHD. Exclusion Criteria: - Treatment on other experimental protocols, if withdrawal of immunosuppression interferes with procedures of follow-up on the primary study. - Leukemia relapse defined as > 5% blasts on bone marrow exam or >1% leukemia cells by immunoflow MRD, or presence of extramedullary leukemia. - History of acute GVHD ≥ stage III or with any degree of active acute or cGVHD. - On steroids for any reason. - Any condition that compromises compliance with the objectives and procedures of this protocol, as judged by the principal investigator. - Cells for DLI cannot be obtained from the donor.

Additional Information

Official title 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
Principal investigator Biljana Horn, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2013.
Information provided to ClinicalTrials.gov by University of California, San Francisco.