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Combining an anti-PD1 antibody with CAR T-cell therapy for young patients with relapsed leukemia

Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence

Phase1; Phase2 Interventional Assistance Publique - Hôpitaux de Paris · NCT05310591

This study is testing if adding a new drug to CAR T-cell therapy can help young patients with relapsed leukemia get better results from their treatment.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment26 (estimated)
Ages1 Year to 25 Years
SexAll
SponsorAssistance Publique - Hôpitaux de Paris Academic / other
Drugs / interventionspembrolizumab, nivolumab, blinatumomab, chemotherapy, immunotherapy, radiation, cyclophosphamide, Fludarabine, CAR T, Chimeric Antigen Receptor
Locations13 sites (Bordeaux and 12 other locations)
Trial IDNCT05310591 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the combination of nivolumab, an anti-PD1 antibody, with tisagenlecleucel, a CAR T-cell therapy, in children, adolescents, and young adults suffering from acute lymphoblastic leukemia (ALL) who have experienced a loss of persistence of CAR T-cells. The study aims to enhance the effectiveness of CAR T-cell therapy by addressing immune-mediated rejection and suppression of T-cell growth. Participants will receive a second infusion of tisagenlecleucel after a reconditioning regimen, with nivolumab administered shortly before the CAR T-cell reinfusion to potentially improve outcomes.

Who should consider this trial

Good fit: Ideal candidates are patients aged 1 to 25 years with a history of relapsed or refractory B-ALL who have previously received tisagenlecleucel and exhibit early loss of B-cell aplasia.

Not a fit: Patients who have not previously been treated with tisagenlecleucel or those with significant organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve the durability of CAR T-cell therapy in young patients with relapsed ALL.

How similar studies have performed: While the combination of CAR T-cell therapy with PD-1 blockade is a novel approach, preclinical data and limited clinical evidence suggest potential benefits, indicating that this strategy is still largely untested in this specific context.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Patients aged from 1 to 25 years (pediatric and young adults) with a history of CD19+ relapsed or refractory B-ALL (any relapse after HSCT, 2nd relapse or later, refractory ALL).
* Patient must have a second tisagenlecleucel (Kymriah ®) product available
* Cohort 1: previously treated by tisagenlecleucel (Kymriah ®), and who present an early loss of B-cell aplasia defined by blood B lymphocytes \< 10 /mm3 and/ or \< 3% of total lymphocytes (\< 6 months after infusion) while still being in CR with undetectable MRD
* Cohort 2: previously treated by tisagenlecleucel (Kymriah ®), who present a loss of B-cell aplasia defined by blood B lymphocytes \< 10 /mm3 and/ or \< 3% of total lymphocytes and a CD19+ ALL detectable disease in the marrow and/or Blood
* Life expectancy \> 12 weeks.
* Karnofsky (age \> 16) Lansky (age \< 16) \> 70 at screening.
* No organ dysfunction
* Who have signed an informed consent
* Affiliation to social security or any health insurance (as a beneficiary or assignee)

Exclusion Criteria:

* Patient has received intervening therapy for leukemia after first tisagenlecleucel infusion (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT).
* Patient has an active autoimmune disease requiring systemic treatment within the past 2 years.
* Patient has known history of, or any evidence of active, non-infectious pneumonitis.
* Patient has a history of non-infectious pneumonitis that required steroid or has current pneumonitis.
* Had receive prior therapy with an anti-PD1, Anti- PDL1 or anti-PDL2 agent.
* Patient has hypersensivity to pembrolizumab/ nivolumab or one of its excipients
* Patient has received a live vaccine injection within 45 days of planned start of study therapy.
* Patients with concomitant genetic syndromes associated with bone marrow failure states: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down syndrome will not be excluded.
* Patients with Burkitt's lymphoma/leukemia
* Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
* Prior treatment with any gene therapy product except first tisagenlecleucel (Kymriah ®) injection.
* 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®)
* Prior anti-cancer monoclonal antibody within 4 weeks before starting the study.
* 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.
* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of Screening), or any uncontrolled infection at Screening.
* Human immunodeficiency virus (HIV) positive test within 8 weeks of Screening.
* Presence of grade 2 to 4 acute or extensive chronic GVHD.
* Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible.
* Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening.
* Previous or concurrent malignancy with the following exceptions:

  * Adequately treated basal cell or squamous cell carcinoma
  * in situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study.
  * A primary malignancy completely resected and in CR for ≥ 5 years
* Pregnant or lactating women (female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion)
* Patient with hypersensivity to Fludarabine and/or cyclophosphamide and/or tisagenlecleucel and/or nivolumab or one of their excipients.

Where this trial is running

Bordeaux and 12 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions B Acute Lymphoblastic LeukemiaAcute Lymphoblastic Leukemia, in Relapse
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.