NCT04697940

Decitabine-primed Tandem CD19/CD20 CAR T Cells Treatment in r/r B-NHL

Decitabine-primed Tandem Targeting CD19 and CD20 Chimeric Antigen Receptor T Cells Treatment in Relapsed and/or Refractory Non-Hodgkin's Lymphoma Patients

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: Han weidong · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, phase 1/2 study has the primary objective of decitabine-primed tandem CART 19/20 in patients with B-NHL who were confirmed as r/r B cell Non-Hodgkin's Lymphoma. A total of 19 to 33 patients are planned to be enrolled and receive decitabine-primed tandem CART 19/20 cell infusion. Phase 1 (9 to 18 cases) is dose escalation part, and phase 2 (10 to 15 cases) is expansion cohort part.

Detailed description

Phase 1 (dose escalation) In phase 1, 9 to 18 subjects will be enrolled. Subjects will receive 3 doses of decitabine-primed tandem CART 19/20 cell therapy (0.5 × 10\^6 cells/kg, 2 × 10\^6 cells/kg, 5 × 10\^6 cells/kg) from low dose to high dose according to the "3 + 3" principle: 1. Three patients were enrolled in the lowest dose group. 2. Subsequent patients were enrolled according to the following rules: 1. If the incidence of dose limiting toxicity (DLT) was 0/3, 3 patients were enrolled in the next high-dose group. 2. If the incidence of DLT was 1/3, 3 patients were enrolled at the same dose; If the incidence of DLT was 1/3 + 0/3, 3 patients were enrolled in the next high-dose group. If the incidence of DLT was 1/3 + 1/3, this dose was defined as maximum tolerated dose (MTD); If the incidence of DLT was 1/3 + 2/3 or 1/3 + 3/3, the previous dose was MTD. 3. If the incidence of DLT was 2/3 or 3/3, the previous dose was MTD. To ensure the safety of the subjects, the first subject in each dose group was observed for at least 28 days after the cell infusion. If no DLT occurred, the remaining two subjects could be enrolled and treated at the same dose level. The safety data of all subjects in each dose group until day 28 should be reviewed and tolerated before proceeding to the next dose group trial. No dose escalation was allowed for the same subject during the trial. If a subject drop out during the observation period due to non-DLT reasons, new subjects should be enrolled to make up for the number of subjects who drop out. Phase 2 (expansion cohort) In phase 2, 10 to 15 subjects will be enrolled and receive decitabine-primed tandem CART 19/20 cell infusion at dose of RP2D, which will be determined based on the MTD, occurrence of DLT, the obtained efficacy results, pharmacokinetics / pharmacodynamics and other data according to the phase 1. \[Objectives\] The primary objectives of the phase 1 were to evaluate the tolerability, safety, and determine recommended phase 2 dose (RP2D). The primary purpose of the phase 2 study was to evaluate the efficacy.

Conditions

• Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma
• Decitabine-primed Tandem CD19/CD20 CAR T Cells

Interventions

Type	Name	Description
BIOLOGICAL	Decitabine-primed Tandem CAR19/20 engineered T cells	Phase I dose escalation (3+3) : dose 1 (0.5 × 10\^6 cells per kg) dose 2 (2 × 10\^6 cells per kg) dose 3 (5 × 10\^6 cells per kg) Phase II: Appropriate dose
DRUG	Fludarabine	Intravenous fludarabine 25-30 mg/m\^2/day on days -5, -4, and -3.
DRUG	Cyclophosphamide	Intravenous cyclophosphamide 300-500 mg/m\^2/day on days -5, -4, and -3.

Timeline

• Start date: 2021-04-15
• Primary completion: 2025-05-31
• Completion: 2026-09-01
• First posted: 2021-01-06
• Last updated: 2025-09-19

Locations

1 site across 1 country: China