Clinical trial · Interventional
Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells
Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells: A Confirmatory, Randomized, Double Blinded Trial
NCT03236129CI-TRIAL-00072335DLI-BoostunknownPhase 3ClinicalTrials.gov clinicaltrialsProvenance
- 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)
The investigators have previously shown the absence of toxicity of Treg-depleted-DLI and the possibility to triggering alloreactivity (GVHD/GVT) in relapsing patients dealing with hematological malignancies who had never shown any signs of GVHD after transplant or after one or more DLI. The Investigators, we plan to demonstrate the benefit of Treg-depleted DLI as compared to the reference treatment of relapse in hematological malignancies after allogeneic HSCT which is currently based on standard DLI
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Hematological Malignancies | Hematopoietic and Lymphoid Cell Neoplasm | PROBABILISTIC | 0.70 |
| Regulatory T Cell Depletion | — | UNRESOLVED | — |
| Relapse | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Standard DLI | Procedure | — | UNRESOLVED |
| T-reg depleted DLI | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Treg depleted DLI
- description
- Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by Treg depleted (Donor Lymphocytes Infusion (DLI)
- interventionNames
- Procedure: T-reg depleted DLI
- type
- ACTIVE_COMPARATOR
- label
- Unmanipulated DLI
- description
- Patients will receive a lymphodepleting treatment combining cyclophosphamide and fludarabine followed by a standard DLI (unmanipulated)
- interventionNames
- Procedure: Standard DLI
Primary outcomes (1)
- measure
- Cumulative incidence of clinical manifestations of GVHD, in the form of acute GVHD with grade ≥ 2 and/or extensive chronic. This parameter will take into account the competitive risk of death unrelated to the GVHD
Eligibility
Eligibility (as posted)
- Sex
- All
Show eligibility criteria text
Inclusion Criteria: * Children and adults regardless of age or weight allograft for primary or secondary acute leukemia, MDS, lympho-proliferative syndrome (CLL, Myeloma, Lymphoma) or myelo-proliferative syndrome. * Prior allogeneic HSCT (myeloablative or non-myeloablative conditioning) from a family donor geno-identical HLA or a volunteer donor HLA 10/10 or 9/10. * Molecular, cytogenetic, cytological relapse regardless of the date after the transplant. * Previous standard DLI should have brought a total dose of at least 5.10\^6 CD3 + / kg (donor HLA-geno idendique) or 2.10\^6 CD3 + / kg (voluntary donor) or 5.10\^5 CD3+/kg (donor haplo-idendique). * Patient corresponding to the failure criteria of a previous standard DLI, defined for each type of hematological malignancies in the test model "DLI-Treg-1" after a delay of at least 30 days in the case of a progressive disease after DLI and at least 60 days in the case of stable disease (due to possible delayed responses after DLI). * Patient consented to the study (the consent of both parents will be collected for minors) * Patients insured by a social security system. * Negative pregnancy test (β-HCG hormone) within the 7 days prior to enrollment Exclusion Criteria: * Presence of acute GVHD grade\> II or extensive chronic GVHD since the first DLI * Patient receiving immunosuppressive therapy for the treatment of GVHD or other reason * Impairment of liver function (transaminases\> 5 N or bilirubin\> 50 µM except Gilbert's disease) or renal function (creatinine clearance \<30 ml / min) * OMS performance status \> 2 * Non controlled severe infection * Patient under tutorship, curatorship or legal protection Donor Inclusion Criteria * Being the initial HSC donor (HLA geno-identical family or haplo-identique or non-family HLA 10/10 or 9/10) * Weight ≥20 kg authorizing the lymphapheresis * Having no contra-indications for donating blood * Absence of severe heart failure, unstable heart disease, uncontrolled hypertension, type 1 diabetes * Negative serology for HIV1-2, HBV, HCV, HTLV 1 and VDRL/TPHA in the 30 days prior to apheresis. Negative viral genomics diagnosis is required for HIV, HBV and HCV * Being informed of the study, and have given an oral non opposition
References
Publications (1)
- BACKGROUNDMaury S, Lemoine FM, Hicheri Y, Rosenzwajg M, Badoual C, Cherai M, Beaumont JL, Azar N, Dhedin N, Sirvent A, Buzyn A, Rubio MT, Vigouroux S, Montagne O, Bories D, Roudot-Thoraval F, Vernant JP, Cordonnier C, Klatzmann D, Cohen JL. CD4+CD25+ regulatory T cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Sci Transl Med. 2010 Jul 21;2(41):41ra52. doi: 10.1126/scitranslmed.3001302. PMID 20650872