Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (10)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Leukemia | Acute Leukemia | ONTOLOGY_EXACT | 0.90 |
| Acute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Biphenotypic Leukemia | — | UNRESOLVED | — |
| Bone Marrow Clonal Malformations | — | UNRESOLVED | — |
| Chronic Myelogenous Leukemia | Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Juvenile Myelomonocytic Leukemia | Juvenile Myelomonocytic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Monosomy 7 | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Withdrawal of immunosuppression and donor lymphocyte infusion | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- NO_INTERVENTION
- label
- Group I: Observation
- description
- 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.
- type
- EXPERIMENTAL
- label
- Group II: Intervention
- description
- 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.
- interventionNames
- Other: Withdrawal of immunosuppression and donor lymphocyte infusion
Primary outcomes (1)
- measure
- Relapse at 2 Years Post-transplant.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 6 Months
- Maximum age
- 25 Years
Show eligibility criteria text
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.
References
Publications (2)
- BACKGROUNDHorn B, Soni S, Khan S, Petrovic A, Breslin N, Cowan M, Pelle-Day G, Cooperstein E, Baxter-Lowe LA. Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies. Bone Marrow Transplant. 2009 Mar;43(6):469-76. doi: 10.1038/bmt.2008.339. Epub 2008 Oct 27. PMID 18955982
- DERIVEDHorn B, Petrovic A, Wahlstrom J, Dvorak CC, Kong D, Hwang J, Expose-Spencer J, Gates M, Cowan MJ. Chimerism-based pre-emptive immunotherapy with fast withdrawal of immunosuppression and donor lymphocyte infusions after allogeneic stem cell transplantation for pediatric hematologic malignancies. Biol Blood Marrow Transplant. 2015 Apr;21(4):729-37. doi: 10.1016/j.bbmt.2014.12.029. Epub 2015 Jan 31. PMID 25644958