Allogeneic Immunotherapy of Hematological Malignancies Using Regulatory T-cell Selective Depletion

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Dec 12, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new approach to treating certain blood cancers, such as leukemia and lymphoma, by using a special form of immunotherapy. The goal is to boost the body's immune response against cancer cells by selectively removing a type of immune cell called regulatory T-cells (Tregs) that can suppress this response. Researchers have found that using a specific marker called CD127 to target Tregs may improve the effectiveness of the treatment compared to previous methods. This trial will focus on patients who have experienced a relapse after receiving a stem cell transplant from a donor and who have not responded well to standard treatments.

To be eligible for this trial, participants must be adults over 18 years old diagnosed with certain blood cancers and have had a prior stem cell transplant. They should also have experienced a relapse and have not had significant success with previous donor lymphocyte infusions (DLI). Participants can expect to provide informed consent and undergo specific assessments before joining the trial. It is important to note that the trial is not yet recruiting participants, and there are several health criteria that could exclude some individuals, such as severe infections or certain liver conditions. Overall, this study aims to explore a promising way to enhance anti-cancer immune responses in patients facing relapsed hematological malignancies.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Adult patient (older than 18 years old without upper limit of age) diagnosed with leukemia, myelodysplasia, myeloproliferative disorder or lymphoproliferative disorder (CLL, myeloma, lymphoma)
• • Previous allogeneic HSCT from a matched sibling, haplo-identical or unrelated donor (any type of conditioning regimen)
• • Haematological relapse (molecular, cytogenetic or cytological) after HSCT
• • Patient refractory (no or partial response) to one or several previous standard unmanipulated DLI
• • Availability of cryopreserved lymphapheresis
• • No loss of chance by using of DLI rather than more incisive anti-tumor agents according to investigator appreciation
• • Written informed consent before any intervention necessary for the trial
• • Affiliation to a social security regime
• • Negative pregnancy test for women of childbearing age participating in the study
• • Effective contraceptive methods for men / women in line with the current CTFG recommendations version 1.1
• Exclusion Criteria:
• • Acute grade ≥ II or moderate/severe chronic GVHD at the time of inclusion
• • Patient receiving immunosuppressive treatment for GVHD or any other reason
• • Creatinine clearance\< 50 ml/min
• • Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) \> 5.0 x upper limit of normal (ULN)
• • Serum total bilirubin \> 50µM (expect for unconjugated hyperbilirubinemia due to Gilbert's disease)
• • Performance status ECOG\>1
• • Severe infection according to CTCAE grading (grade\>2)
• • Pregnant or lactating women
• • Patient under tutorship, curatorship or legal protection
• • Ongoing participation in another interventional research protocol within the same field of immune modulation (through cell therapy or not)
• • State medical aid