Depleting regulatory T cells to improve treatment for blood cancers
Allogeneic Immunotherapy for Hematological Malignancies by Selective Depletion of Regulatory T Cells: A Confirmatory, Randomized, Double Blinded Trial
This study is testing if a new type of donor cell treatment without regulatory T cells can help patients with blood cancers who have relapsed after a stem cell transplant feel better compared to the standard treatment.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 52 (estimated) |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | cyclophosphamide, fludarabine |
| Locations | 1 site (Creteil) |
| Trial ID | NCT03236129 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the effectiveness of Treg-depleted donor lymphocyte infusion (DLI) compared to standard DLI in patients with hematological malignancies who have relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). Participants will be randomized to receive either the experimental Treg-depleted DLI or the control unmanipulated DLI, following a lymphodepleting treatment. The study focuses on patients who have not experienced graft-versus-host disease (GVHD) after previous treatments. The goal is to demonstrate a significant benefit in managing relapses in these patients.
Who should consider this trial
Good fit: Ideal candidates include children and adults with hematological malignancies who have previously undergone allogeneic HSCT and have not responded to standard DLI.
Not a fit: Patients who have experienced GVHD or those who have not undergone prior allogeneic HSCT may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a more effective treatment option for patients with relapsed hematological malignancies.
How similar studies have performed: Previous studies have indicated the potential of Treg depletion in enhancing immune responses, suggesting a promising avenue for this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Creteil
- Henri Mondor Hospital — Creteil, France (Recruiting)
Study contacts
- Principal investigator: Florence BEKCERICH, MD — Assistance Publique - Hôpitaux de Paris
- Study coordinator: Florence BECKERICH, MD
- Email: florence.beckerich@aphp.fr
- Phone: (0)1 49 81 20 57
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.