Status:
RECRUITING
Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence
Lead Sponsor:
Assistance Publique - Hôpitaux de Paris
Conditions:
B Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia, in Relapse
Eligibility:
All Genders
1-25 years
Phase:
PHASE1
PHASE2
Brief Summary
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 ...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
March 15 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2027
Estimated Enrollment :
26 Patients enrolled
Trial Details
Trial ID
NCT05310591
Start Date
March 15 2023
End Date
March 1 2027
Last Update
May 29 2024
Active Locations (13)
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1
CHRU Bordeaux
Bordeaux, France
2
CHRU Lille
Lille, France
3
HCL - Lyon Sud
Lyon, France
4
HCL
Lyon, France