CAR-T-19 Cells for Patients With CD19+ Relapse/Refractory B-ALL

A Single-arm, Open-label Phase I Study of CAR-T-19 (Anti CD19 scFv Chimeric Antigen Receptor T) Cells for Patients With CD19-positive Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia Under The Age of 25

This is a single-arm, open-label phase I study to determine the safety, tolerability, and recommended dose (RD) of CAR-T-19 cells for patients with CD19+ relapse/refractory B-ALL under the age of 25.

Study Overview

• Status: Recruiting
• Conditions: CD19+ Relapse/Refractory B-ALL
• Intervention / Treatment: Biological: CAR-T-19 Cells

Detailed Description

B-cell acute lymphoblastic leukemia (B-ALL) accounting for 85% of all ALL cases, is a common hematological malignancy in children and adults. CD19 is a widely expressed antigen in both normal B cells and B cells-derived leukemia and lymphomas. This is a single-arm, open-label phase I study of CAR-T-19 (anti CD19 scFv chimeric antigen receptor T) cells for patients with CD19-positive relapse/refractory B-ALL under the age of 25.

Primary endpoint is to determine the safety, tolerability, and recommended dose (RD) of CAR-T-19. Secondary endpoints measure ORR, OS and others.

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daihong Liu; Phone Number: +8613681171597; Email: daihongrm@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Daihong Liu; Phone Number: +8613681171597; Email: daihongrm@163.com
      • Principal Investigator: Daihong Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with relapse/refractory B-ALL.
• Tumor cells from bone marrow or peripheral blood are measured CD19+ with 3 months before enrollment.
• Karnofsky Score ≥ 70 or Lansky Score ≥ 50.
• Patients who have a life expectancy of at least 12 weeks.
• Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures.

Exclusion Criteria:

• Patients with extramedullary relapse (EMR).
• Patients with genetic diseases, Burkitt lymphoma and leukemia or other malignancies.
• Patients positive for any of the following: HbsAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA.
• Patients with other uncontrolled infection.
• Patients who received anti-CD19 / anti-CD3 therapy, or any other anti-CD19 therapy.
• Patients with active Grade II-IV GVHD within 3 months prior to screening.
• Tumor cells are detected in cerebrospinal fluid.
• Patients who received HSCT within 3 months prior to screening.
• Anticipated other clinical trials within 4 weeks before this trial
• Pregnant or lactating women.
• Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T-19 Cells; The patients with CD19+ relapse or refractory B-ALL will receive a single infusion of autologous CAR-T-19 cells, with the escalated dose ranging from 0.5×10^6/kg to 5.0×10^6/kg CAR+ cells.	Biological: CAR-T-19 Cells; T cells were isolated from the PBMC of patients, transduced with lentivirus, expanded in vitro, and infused into patients. The escalated doses include 0.5×10^6/kg,1.5×10^6/kg, 5.0×10^6/kg CAR+ cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	DLT within 28 days (±3 days) after CAR-T-19 infusion.	up to 2 years
Maximum tolerated dose (MTD)	The maximum dose of DLT occurred in ≤1/6 of the subjects within 28 days (±3 days) after CAR-T-19 infusion.	up to 2 years
Adverse events	Percentage of subjects with adverse events.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall recovery rate (ORR)	Percentage of subjects who achieved complete response (CR) and incomplete hematologic recovery (CRi) for the first time at Day 28 and Day 90 after CAR-T-19 infusion.	up to 2 years
MRD-Negative Rate	Percentage of subjects with MRD-negative CR and incomplete blood and MRD-negative CRi for the first time at Day 28 and Day 90 after CAR-T-19 infusion.	up to 2 years
Duration of Response (DOR)	The time from achieving CR and CRi for the first time to recurrence or death from any cause	up to 2 years
Progression-free Survival (PFS)	The time from CAR-T-19 infusion to recurrence, progression or death from any cause, whichever occurs first.	up to 2 years
Overall survival (OS)	The time from CAR-T-19 infusion to death from any cause.	up to 2 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Daihong Liu, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2021
• Primary Completion (Anticipated): July 15, 2022
• Study Completion (Anticipated): September 16, 2024

Study Registration Dates

• First Submitted: February 26, 2022
• First Submitted That Met QC Criteria: February 26, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: February 26, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; B-ALL
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence
• Other Study ID Numbers: CT19-ALL-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No