Allogeneic CD19-targeted CAR-γδT Cell Infusion Therapy in Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia

November 17, 2024 updated by: The First Affiliated Hospital of Soochow University

Assessment of the Safety and Efficacy of Allogeneic CD19-targeted CAR-γδT Cell Infusion Therapy in Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia: A Single-Arm, Open-Label, Prospective Study

This clinical trial aims to investigate the safety, optimal dosage, and effectiveness of allogeneic CD19-targeted CAR-γδT Cell in treating CD19-positive relapsed/refractory B-ALL

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary Objective:

To assess the safety of allogeneic CD19-targeted CAR-γδT Cell in the treatment of relapsed/refractory B-ALL, and to determine the recommended dose (RP2D) for the phase II study.

Secondary Objective:

To evaluate the efficacy of allogeneic CD19-targeted CAR-γδT Cell in the treatment of relapsed/refractory B-ALL.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • China, Jiangsu
      • Suzhou, China, Jiangsu, China
        • Recruiting
        • The First Affiliated Hospital of Soochow University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥14 years, gender not specified;
  2. Diagnosed with B-ALL according to the World Health Organization (WHO) classification of hematopoietic and lymphoid tissue tumors (2022 version);
  3. Meet the diagnosis of relapsed/refractory leukemia, excluding isolated extramedullary relapse; For relapsed or refractory B-ALL, including any of the following situations: a) Relapse: Peripheral blood or bone marrow recurrence of primitive cells >5% or extramedullary lesions appear again after complete remission; b) Refractory: Primary refractory patients who fail to achieve complete remission after standard induction chemotherapy；those with positive measurable residual disease can also be included；
  4. Flow cytometry confirms positive CD19 expression in leukemia cells；
  5. Estimated survival >3 months;
  6. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;

  7. The vital organs function in accordance with the following requirements:

    7.1Left ventricular ejection fraction (LVEF) ≥50%; 7.2Pulmonary function：normal oxygen saturation without oxygen supplementation; 7.3Total bilirubin (TBil) ≤3×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN； 7.4Creatinine ≤1.5×ULN;

  8. Pregnancy test must be negative, and fertile non-abstinent female patients must agree to use effective contraception from the start of self-screening to 1 year after cell infusion. Fertile male patients with fertile partners must agree to use effective contraception from the start of self-screening to 1 year after cell infusion, and should not donate semen or sperm throughout the study period；
  9. No obvious hereditary diseases；
  10. The subject and their legal guardian voluntarily participate in this study, understand the trial information and objectives, and provide informed consent with a signed and dated signature.

Exclusion Criteria:

  1. Patients with severe autoimmune diseases or immunodeficiency diseases;
  2. Patients with a history of severe central nervous system diseases, such as uncontrolled seizures, stroke, severe brain injury resulting in aphasia, paralysis, dementia, Parkinson's disease, psychiatric disorders, etc.;
  3. Any unstable diseases occurring within screening period (including but not limited to): unstable angina, ischemic or cerebrovascular accidents, myocardial infarction, severe arrhythmias requiring drug treatment (such as rapid atrial fibrillation, high-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation, or torsades de pointes), cardiac catheterization or coronary artery stenting, or coronary artery bypass surgery, thrombotic or embolic events.
  4. Active graft-versus-host disease requiring continued systemic therapy;
  5. The presence of anti-FMC63 and a positive DSA reaction;
  6. Patients who have previously received CAR-T cell therapy within 6 months or donor lymphocyte infusion within 6 weeks before screening;
  7. History of or concomitant active malignant tumors, excluding cured non-invasive basal cell or squamous cell skin cancer, uterine cervical carcinoma in situ or localized prostate cancer or breast ductal carcinoma in situ without recurrence for at least 2 years;
  8. Presence of other severe medical conditions as determined by the investigator, such as uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.;
  9. Other severe or persistent active infections;
  10. Other conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients with relapsed/refractory B cell Acute lymphoblastic Leukemia
In this study, we adopted a 3+3 design with dose escalation. A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, and each dose group received treatment on Days 0 through i.v. injection, with bone marrow examination performed on Days 14 and 28 to assess tumor burden. Upon assessment by the investigators and discussion with the Safety Review Committee (SRC), it will be determined that whether patients may benefit from additional infusions. With SRC approval, the number of administrations could be increased. At the end of dose escalation, the SRC may decide to adjust the number of participants in the designated dose group as deemed appropriate.
Biological: QH10304-BAL-01
dose escalation (3+3) : dose 1 (3 × 10^8cells/kg) ,dose 2 (1 × 10^9 cells/kg) ,dose 3 (3 × 10^9cells/kg)
Drug: Fludarabine
Intravenous fludarabine 30mg/m2 on days-6 to -3,the infusion dose is adjusted according to the subject's condition
Drug: Cyclophosphamide
Intravenous cyclophosphamide 1000mg/m2 on days -5 to -3, the infusion dose is adjusted according to the subject's condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose limiting toxicity (DLT)
Time Frame: within 28 days after receiving the infusion
  • Grade ≥ 4 CRS, or Grade 3 CRS that has not resolved to Grade 1 or 2 within 7 days of onset;
  • Grade 4 ICANS or Grade 3 ICANS lasting ≥ 96 hours;
  • Other Grade 3 or higher AEs associated with allogeneic CD19-targeted CAR-γδT Cell and lasting ≥ 7 days.
within 28 days after receiving the infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Soochow University

Investigators

  • Study Chair: Xiaowen Tang, Ph.D, The First Affiliated Hospital of Soochow University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

November 17, 2024

First Submitted That Met QC Criteria

November 17, 2024

First Posted (Estimated)

November 20, 2024

Study Record Updates

Last Update Posted (Estimated)

November 20, 2024

Last Update Submitted That Met QC Criteria

November 17, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QH10304-BAL-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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