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

NCT06696833 | Recruiting Early Phase 1

• 1 other identifier: QH10304-BAL-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

B-Cell Acute Lymphoblastic Leukemia, Adult

Keywords

B-ALL

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  * 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

Study Arms (1)

Patients with relapsed/refractory B cell Acute lymphoblastic Leukemia

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

QH10304-BAL-01 BIOLOGICAL

dose escalation (3+3) : dose 1 (3 × 10\^8cells/kg) ,dose 2 (1 × 10\^9 cells/kg) ,dose 3 (3 × 10\^9cells/kg)

Patients with relapsed/refractory B cell Acute lymphoblastic Leukemia

Fludarabine DRUG

Intravenous fludarabine 30mg/m2 on days-6 to -3,the infusion dose is adjusted according to the subject's condition

Patients with relapsed/refractory B cell Acute lymphoblastic Leukemia

Cyclophosphamide DRUG

Intravenous cyclophosphamide 1000mg/m2 on days -5 to -3, the infusion dose is adjusted according to the subject's condition

Patients with relapsed/refractory B cell Acute lymphoblastic Leukemia

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥14 years, gender not specified;
• Diagnosed with B-ALL according to the World Health Organization (WHO) classification of hematopoietic and lymphoid tissue tumors (2022 version);
• 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；
• Flow cytometry confirms positive CD19 expression in leukemia cells；
• Estimated survival \>3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
• The vital organs function in accordance with the following requirements:
• Left 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;
• 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；
• No obvious hereditary diseases；
• 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.

You may not qualify if:

• Patients with severe autoimmune diseases or immunodeficiency diseases;
• 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.;
• 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.
• Active graft-versus-host disease requiring continued systemic therapy;
• The presence of anti-FMC63 and a positive DSA reaction;
• Patients who have previously received CAR-T cell therapy within 6 months or donor lymphocyte infusion within 6 weeks before screening;
• 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;
• Presence of other severe medical conditions as determined by the investigator, such as uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.;
• Other severe or persistent active infections;
• Other conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, China, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Xiaowen Tang, Ph.D

  The First Affiliated Hospital of Soochow University

  STUDY CHAIR

Central Study Contacts

Xiaowen Tang, Ph.D

CONTACT

(0086)051267780086; xwtang1020@163.com

Depei Wu, Ph.D

CONTACT

(0086)051267780086; drwudepei@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2024
• First Posted: November 20, 2024
• Study Start: December 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

CN (1)