Combination of an Anti-PD1 antibody with CART cells Reinfusion in children, adolescents and young adults with Acute Lymphoblastic Leukemia after loss of persistence CAPTiRA

Phase 1

Conditions: Relapsed or refractory B-ALL (any relapse after HSCT, 2nd relapse or later, refractory ALL), aged 1-25 years old, previously treated by Tisagenlecleucel (Kymriah ®), Cohort 1 presenting early loss of B cell aplasia (< 6 months after infusion) And being in MRD negative complete remission orCohort 2: presenting loss of B cell aplasia and having detectable marrow and/or blood CD19+ ALL cells.
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2021-003035-28-FR

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 26

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) > 50 at screening.
•No organ dysfunction
•Who have signed an informed consent
•Affiliation to social security or any health insurance (as a beneficiary or assignee)

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patient has received intervening therapy for leukemia after first Tisagenlecleucel infusion.
•Patient has an active auto-immune 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 30 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., = Grade
1 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:
oAdequately treated basal cell or squamous cell carcinoma
oIn situ carcinoma of the cervix or breast, treated curatively and without evidence ofrecurrence for at least 3 years prior to the study.
oA 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)