Clinical Trials Logo

Clinical Trial 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


Clinical Trial Description

n/a


Study Design


Related Conditions & MeSH terms


NCT number NCT05310591
Study type Interventional
Source Assistance Publique - Hôpitaux de Paris
Contact Andre Baruchel, Pr
Phone +331 40 03 53 88
Email andre.baruchel@aphp.fr
Status Recruiting
Phase Phase 1/Phase 2
Start date March 15, 2023
Completion date March 2027

See also
  Status Clinical Trial Phase
Completed NCT05557110 - Reduced-dose Chemotherapy Followed by Blinatumomab in Induction Therapy of Newly Diagnosed Non-elderly Ph-B-ALL Phase 2
Recruiting NCT04872790 - Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia Phase 1
Active, not recruiting NCT02458014 - Blinatumomab in Treating Patients With B-cell Acute Lymphoblastic Leukemia With Minimal Residual Disease Phase 2
Active, not recruiting NCT03233854 - CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies Phase 1
Recruiting NCT03959085 - Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy Phase 3
Recruiting NCT03856216 - Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Leukemia or Lymphoma Undergoing Stem Cell Transplantation Phase 2
Recruiting NCT03241940 - Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies Phase 1
Active, not recruiting NCT02484430 - Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia Phase 2
Active, not recruiting NCT02146924 - Cellular Immunotherapy in Treating Patients With High-Risk Acute Lymphoblastic Leukemia Phase 1
Recruiting NCT02877303 - Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia Phase 2
Terminated NCT03488225 - Combination Chemotherapy and Inotuzumab Ozogamicin in Treating Patients With B Acute Lymphoblastic Leukemia Phase 2
Recruiting NCT02968472 - A Phase I Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Leukemia Phase 1
Recruiting NCT05157971 - Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia Phase 1
Active, not recruiting NCT02143414 - Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia Phase 2
Completed NCT03289455 - CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL) Phase 1/Phase 2
Suspended NCT03150693 - Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia Phase 3
Not yet recruiting NCT06317662 - Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia Phase 2
Recruiting NCT03914625 - A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia Phase 3
Not yet recruiting NCT06124157 - A Study Comparing the Combination of Dasatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or Philadelphia Chromosome-Like (Ph-Like) ABL-Class B-Cell Acute Lymphoblastic Leukemia (B-ALL) Phase 3
Withdrawn NCT02538926 - Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma Phase 2