OncoMatch/Clinical Trials/NCT05310591
Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence
Is NCT05310591 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Decreasing starting times for beginning nivolumab (Time to Event Continual Reassessment Method (TITE-CRM) ) and Nivolumab starting at day -1 for b acute lymphoblastic leukemia.
Treatment: Decreasing starting times for beginning nivolumab (Time to Event Continual Reassessment Method (TITE-CRM) ) · Nivolumab starting at day -1 — Tisagenlecleucel (CTL019) is an anti-CD19 autologous Chimeric Antigen Receptor (CAR) T-cell therapy, which has shown dramatic early results in advanced ALLs. Early loss of B-cell aplasia (recovery of B-cells in marrow/ peripheral blood within 6 months after infusion), a marker of the loss or non-functionality of the CAR T-cells, is associated to a very high risk of relapse. A reinfusion of CTL019, even after Fludarabine-Cyclophosphamide reconditioning, frequently fails to induce further expansion as observed in UPENN studies and in the Robert Debré Hospital experience. Non-persistence of CAR T-cells may be due to immune- mediated rejection or environment-mediated suppression of their growth. Evidence for increased PD-1 expression in CAR T-cells between infusion and peak expansion has been demonstrated in clinical samples. Preclinical data and few clinical data support a role of PD- 1-PD-L1 blockade in improving the effectiveness of CAR T-cell therapy. The objectives of this phase I/II study is to determine the safety, efficacy and feasibility of Nivolumab (Opdivo®)- an anti-PD1 treatment- combined to tisagenlecleucel in a cohort of relapsed or refractory B-ALL patients, aged 1-25 years old, previously treated by tisagenlecleucel (Kymriah®), with a demonstrated early loss of B-cell aplasia (within 6 months), a surrogate marker of the loss of CAR T-cells or their non- functionality. More specifically, the main objectives are: • In cohort 1 that includes patients with a MRD negative disease status combined to an early loss (within 6 months) of B-cell aplasia : To determine the optimal starting time of Nivolumab (Opdivo®) in terms of safety and efficacy among 4 candidate time points (day 14, day 11, day 5, and day - 1). • In cohort 2 that includes relapsed patients with an early loss (within 6 months) of B-cell aplasia : To estimate the feasibility in terms of safety and efficacy of a very early start of nivolumab (day-1), prior to the reinfusion of tisagenlecleucel
Check if I qualifyExtracted eligibility criteria
Cancer type
Acute Lymphoblastic Leukemia
Biomarker criteria
Required: CD19 positive
Prior therapy
Must have received: CAR-T cell therapy (tisagenlecleucel)
previously treated by tisagenlecleucel (Kymriah ®)
Cannot have received: any intervening therapy for leukemia after first tisagenlecleucel infusion (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT)
Patient has received intervening therapy for leukemia after first tisagenlecleucel infusion (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT)
Cannot have received: anti-PD-1 therapy
Had receive prior therapy with an anti-PD1, Anti- PDL1 or anti-PDL2 agent
Cannot have received: gene therapy product
Exception: except first tisagenlecleucel (Kymriah ®) injection
Prior treatment with any gene therapy product except first tisagenlecleucel (Kymriah ®) injection
Cannot have received: anti-CD19/anti-CD3 therapy
Exception: except for patients pre-treated with blinatumomab and/or tisagenlecleucel (Kymriah®)
Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab and/or tisagenlecleucel (Kymriah®)
Cannot have received: anti-cancer monoclonal antibody
Exception: within 4 weeks before starting the study
Prior anti-cancer monoclonal antibody within 4 weeks before starting the study
Cannot have received: chemotherapy
Exception: within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent
Cannot have received: targeted small molecule therapy
Exception: within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent
Cannot have received: radiation therapy
Exception: within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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