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

Status: Recruiting
Location: See all (13) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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 B-cells in marrow/ peripheral blood within 6 months after infusion), a marker of the loss or non-functionality of the CAR T-cells, is associated to a very high risk of relapse. A reinfusion of CTL019, even after Fludarabine-Cyclophosphamide reconditioning, frequently fails to induce further expansion as observed in UPENN studies and in the Robert Debré Hospital experience. Non-persistence of CAR T-cells may be due to immune- mediated rejection or environment-mediated suppression of their growth. Evidence for increased PD-1 expression in CAR T-cells between infusion and peak expansion has been demonstrated in clinical samples. Preclinical data and few clinical data support a role of PD- 1-PD-L1 blockade in improving the effectiveness of CAR T-cell therapy. The objectives of this phase I/II study is 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

Eligibility
Participation Requirements
Sex: All
Minimum Age: 1
Maximum Age: 25
Healthy Volunteers: f
View:

• 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)

Locations
Other Locations
France
CHRU Bordeaux
RECRUITING
Bordeaux
CHRU Lille
RECRUITING
Lille
HCL
RECRUITING
Lyon
HCL
RECRUITING
Lyon
HCL - Lyon Sud
RECRUITING
Lyon
Hôpital pour enfants - La Timone
RECRUITING
Marseille
CHU Montpellier - Hopital Arnaud de Villeneuve
RECRUITING
Montpellier
CHU Nancy
RECRUITING
Nancy
CHU Nantes - Hopital Mère-enfants
RECRUITING
Nantes
Robert Debre hospital
RECRUITING
Paris
Saint Louis hospital
RECRUITING
Paris
CHU Rouen
RECRUITING
Rouen
CHRU Strasbourg
RECRUITING
Strasbourg
Contact Information
Primary
Andre Baruchel, Pr
andre.baruchel@aphp.fr
+331 40 03 53 88
Backup
Jérôme Lambert, Pr
jerome.lambert@u-paris.fr
+33142499742
Time Frame
Start Date: 2023-03-15
Estimated Completion Date: 2027-03
Participants
Target number of participants: 26
Treatments
Experimental: Patients with MRD negative disease status: Time to Event Continual Reassessment Method (TITE-CRM)
Experimental: For relapsed patients
Sponsors
Leads: Assistance Publique - Hôpitaux de Paris

This content was sourced from clinicaltrials.gov

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