NCT04499573

Bispecific CD19/CD22 CAR-T for Treatment of Children and Young Adults With r/r B-ALL

Safety and Efficiency of Anti-CD19/CD22 Tandem Fully Human Chimeric Antigen Receptor (CAR)-Transduced T-cell Therapy for Pediatric and Young Adult Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia: a Single Centre, Non-randomised, Open Label Phase I-II Clinical Trial of Automatically Produced Cell Therapy Product MB-CAR-T19-22 Using CliniMACS Prodigy

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology · Academic / Other
• Sex: All
• Age: 3 Months – 25 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the safety and efficiency of autologous CD19/CD22 CAR-T lymphocytes in a cohort of pediatric and young adult patients with relapsed /refractory B-lineage acute lymphoblastic leukemia

Detailed description

The main objectives of the study are: * To investigate the incidence of adverse events of grade 3-5 within after CD19/CD22 CAR lymphocyte infusion by day 28, * To evaluate the incidence of complete remission and MRD-negative CR by day 28 * To evaluate the long-term effectiveness of CD19/CD22 CAR-T therapy (cumulative incidence of relapse, event-free survival, overall survival) at 1, 2, and 5 years after infusion. * To evaluate the persistence of CD19/CD22 CAR-T cells and duration of B-cell aplasia (\<1% B-cells in the blood) and hypogammaglobulinemia In order to prevent the development of CRS, all patients will receive an infusion of tocilizumab at 8 mg/kg body weight on day 0 before CAR-T cells infusion. Step-down and step-up dosing will be used to adapt the trial to the scenario of excess toxicity and/or suboptimal effect. Reevaluation of dosing will be done for each cohort separately after the enrollment 5th study subject reaches day 28 or earlier if the threshold for excess toxicity or suboptimal effect is achieved. Based on interim analysis in March 2021 after the enrollment 5th study subject reaches day 28 study population will be divided into three cohorts: 1. CD19-positive (both CD19 and CD22 expressed on over 50% of leukemia cells), low and high disease burden. 2. CD19-negative (CD22 expressed on over 50% of leukemia cells) low and high disease burden; 3. Allogeneic HSCT+ allogeneic CAR-T cohort

Conditions

• B-ALL

Interventions

Type	Name	Description
DRUG	CD19/CD22 CAR-T	The treatment plan will be based on stratification by the initial leukemia burden. Patients with "low disease burden" will receive a lymphodepletion chemotherapy of fludarabine (total dose 120mg/m2) and cyclophosphamide (total dose 750mg/m2) over 5 days. Patients will "high disease burden" will receive a lymphodepletion chemotherapy of fludarabine (total dose 120 mg/m2), cyclophosphamide (total dose 750 mg/m2), cytarabine (total dose 900 mg/m2), etoposide (total dose 450 mg/m2), dexamethasone (total dose 30 mg/m2) over 5 days. Based on interim analysis the following dosing approach will be implemented starting April 2021: Cohort 1: CD19+ disease, low and high burden: 1st dose - 150k/kg, 2nd dose - 850k/kg Cohort 2: CD19- disease, low and high burden: 1st dose - 500k/kg, 2nd dose - 500k/kg Cohort 3: HSCT+CAR-T: 100k/kg

Timeline

• Start date: 2020-07-27
• Primary completion: 2022-03-13
• Completion: 2027-03-13
• First posted: 2020-08-05
• Last updated: 2023-02-22

Locations

1 site across 1 country: Russia