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

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Apr 4, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for children, adolescents, and young adults aged 1 to 25 years who have a type of blood cancer called Acute Lymphoblastic Leukemia (B-ALL) that has come back or has not responded to previous treatments. The trial is testing the combination of a medication called Nivolumab (Opdivo®), which helps boost the immune system, with a type of cell therapy known as Tisagenlecleucel (Kymriah®). This study specifically focuses on patients who have shown early signs that their cancer treatment is not working as well as hoped, indicated by a loss of certain immune cells called B-cells within six months of their last treatment.

To be eligible for this trial, participants must have a history of relapsed or treatment-resistant B-ALL and must have a second dose of Tisagenlecleucel available. The trial aims to determine the safest and most effective timing for giving Nivolumab alongside the Tisagenlecleucel reinfusion. Participants can expect close monitoring for safety and effectiveness throughout the study. If you or a loved one meet the eligibility criteria and are interested, this trial may provide an opportunity to explore a potentially promising treatment for a challenging condition.

Gender

ALL

Eligibility 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.