Modified CD19 CAR-T in Patients With Relapsed or Refractory CD19+ B-cell Malignancies

Phase I, Open Label, Study of CXCR4 Modified CD19 CAR-T Therapy in Patients With Relapsed or Refractory CD19+ B-cell Malignancies

This study aims to evaluate the safety and tolerance of modified CD19 CAR T cells in treating refractory/relapsed B-cell malignancies. CAR-T cells will be investigated as a single agent both in relapsed/refractory B-cell acute lymphoblastic leukaemia (B-ALL) and up to 60% of patients with B-cell non-Hodgkin's lymphoma (NHL).

Study Overview

• Status: Recruiting
• Conditions: Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Leukemia
• Intervention / Treatment: Biological: Modified anti-CD19 CAR T cells

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: FUCHUN GUO, MD; Phone Number: +86(028)85423525; Email: FCguo0797@wchscu.cn
• Study Contact Backup: Name: pei shu, MD; Phone Number: +86(028)85423525; Email: peishu1991@sina.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China
      • Recruiting
      • Sichuan University
      • Contact: weiming li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female aged 18-70 years;
2. Estimated survival time ≥ 12 weeks;

3. Histologically confirmed diagnosis of CD19+ B-ALL or CD19+ B-NHL(meeting one of the following conditions):

   1. Ineffectively or relapses after 2 or more remedial treatments
   2. Relapse after auto-HSCT or unsuitable for auto-HSCT;
4. At least one assessable tumor lesion;
5. ECOG performance status 0 to 2;
6. Creatinine clearance rate≥ 60 ml/min, ALT and AST ≤ 2.5 times of upper limit of normal, total bilirubin ≤ 1.5 times of upper limit of normal;
7. Male and female of reproductive potential must agree to use birth control during the study and for at least 30 days post study;
8. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

1. Patients with other uncontrolled malignancies;
2. Previously treated with any CAR-T cell product or other genetically-modified T cell therapy;
3. Patients with HIV infection, hepatitis B (HBsAg positive) or hepatitis C（anti-HCV positive);
4. Patients with central nervous system involvement by lymphoma ,malignant cells in cerebrospinal fluid or history of brain metastasis;
5. Patients with atrial or ventricular involvement by B-cell malignancies;
6. Patients with tumor mass require urgent treatment, such as ileus or vascular compression;
7. Patients with severe disease or other uncontrolled diseases that were not suitable for this trial, such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, grade 2-3 hypertension;
8. Unstable pulmonary embolism, deep venous embolism, or other major arterial/venous thromboembolism events occurred within 30 days prior to randomization. If patients receive anticoagulant therapy, the treatment dose must be stable prior to randomization;
9. Any situations that the investigators believes were not suitable for this trial;
10. Long-term use of immunosuppressive agents after organ transplantation, except for the patients recently or currently receiving inhaled steroids;
11. Pregnant(or lactation) women;
12. Patients with severe active infections(excluding simple urinary tract infection and bacterial pharyngitis)within 30 days prior to randomization

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: Modified anti-CD19 CAR T cell therapy; CAR T cell therapy	Biological: Modified anti-CD19 CAR T cells; intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events [Safety and Tolerability]	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Up to 5 years after modified CD19 CAR-T cells infusion
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after modified CD19 CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B-cell malignancies, Overall response rate(ORR)	Assessment of ORR(ORR=CR+PR)	3 months, 6 months
B-cell malignancies, Overall survival	From the first infusion of modified CD19 CAR-T cells to death or the last visit	Up to 2 years after modified CD19 CAR-T cells infusion
B-cell malignancies, progression-free survival（PFS）	From the first infusion of modified CD19 CAR-T cells to the occurrence of any event, including death, relapse, disease progression, and the last visit	Up to 2 years after modified CD19 CAR-T cells infusion
B-cell malignancies, disease control rate (DCR)	Assessment of DCR(DCR=CR+PR+SD)	Month 6,12,18 and 24

Collaborators and Investigators

• Sponsor: Liqun Zou
• Investigators: Principal Investigator: liqun zou, phd, Sichuan University

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: December 21, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 24, 2020

Study Record Updates

• Last Update Posted (Actual): September 26, 2022
• Last Update Submitted That Met QC Criteria: September 22, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Modified CD19 CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: MCART-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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