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CAPTIRALL _ Combination of an Anti-PD1 antibody with CART cells Reinfusion in children, adolescents and young adults with Acute Lymphoblastic Leukemia after loss of persistence
EU CTIS ID: 2024-514345-11-00
What this study is testing
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 These objectives will be evaluated on the two following co-primary endpoints: 1. Limiting-toxicities between infusion and D28; 2. Efficacy, which evaluation is delayed at M3 after tisagenlecleucel reinfusion and defined by MRD negative CR AND B cell aplasia
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- • 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 and/or CSF
- • Life expectancy > 12 weeks.
- • Karnofsky (age > 16) Lansky (age < 16) > 70 at screening.
You likely can't join if
- • Patient has received intervening systemic therapy* for leukemia after first tisagenlecleucel infusion. (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT) *systemic therapies exclude intrathecal therapy
- • Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines at the time of reinfusion of CAR T cells. 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.
- • Patient has an active autoimmune disease requiring systemic treatment within the past 2 years.
- • Previous or concurrent malignancy with the following exceptions: o Adequately treated basal cell or squamous cell carcinoma o In situ carcinoma of the cervix or breast, treated curatively and without evidence ofreccurrence of at least 3 years prior to the trial o A primary malingnacy completelyresected and in CR for ≥ 5 years
- • Pregnant or lactating women (female trial 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.
See the full eligibility 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 and/or CSF
- • 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)
- • Patient has received intervening systemic therapy* for leukemia after first tisagenlecleucel infusion. (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT) *systemic therapies exclude intrathecal therapy
- • Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines at the time of reinfusion of CAR T cells. 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.
- • Patient has an active autoimmune disease requiring systemic treatment within the past 2 years.
- • Previous or concurrent malignancy with the following exceptions: o Adequately treated basal cell or squamous cell carcinoma o In situ carcinoma of the cervix or breast, treated curatively and without evidence ofreccurrence of at least 3 years prior to the trial o A primary malingnacy completelyresected and in CR for ≥ 5 years
- • Pregnant or lactating women (female trial 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.
- • 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 trial therapy.
- • Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
- • 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
- Patient with hypersensivity to Fludarabine and/or cyclophosphamide and/or tisagenlecleucel and/or nivolumab or one of their excipients.
- • 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 trial.
- • Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to reinfusion of CAR T cells 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.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.