Clinical Study of Universal CD19 CAR-γδ T Cell Infusion in the Treatment of Relapsed/Refractory Acute B Lymphoblastic Leukemia

Overview

This study is an open-label, single-arm clinical trial designed to evaluate the safety and tolerability of QH103 cell infusion in subjects with CD19-positive R/R B-ALL.

Interventions

• Drug Cyclophosphamide
  Eligible subjects will undergo lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises cyclophosphamide (500-1000 mg/m² administered 3 days).
• Drug Fludarabine
  Eligible subjects will receive lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises fludarabine (30-40 mg/m² administered 3 days).
• Biological QH103 Cell Injection
  Biological: CD19 CAR-γδT cell Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with dose escalation (3+3) : dose 1 (1×10\^8 CAR+cells) ,dose 2 (3× 10\^8 CAR+cells).

Primary outcome measures

• Adverse Event [Time frame: 12 months]
• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: 28 days]

Secondary outcome measures (3)

• PK(Pharmacokinetics):Number and Copy Number of CD19 CAR-γδT cells [Time frame: 12 months]
• PK: Persistence of CD19 CAR-γδT [Time frame: 12 months]
• PD(Pharmacodynamics) ：Changes in Various Cytokine Levels (IL-2, IL-4, IL-6, IFN-γ, TNF α, etc.) from Baseline [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Age > 14 years, gender unrestricted;
• Clinically diagnosed with relapsed/refractory acute B-lymphoblastic leukemia, with bone marrow blast/immature lymphocyte proportion ≥5% (morphology) (excluding cases with isolated extramedullary involvement), meeting any of the following criteria:

• Failure to achieve CR after 2 cycles of standard chemotherapy;
• Initial induction achieved CR, but CR duration ≤12 months;
• Relapsed/refractory B-ALL refractory to first or multiple salvage therapies;
• Post-hematopoietic stem cell transplantation relapse, including hematological relapse and minimal residual disease (MRD) positivity;
• Patients for whom no standard therapy exists.
• Cytology or histology confirms tumor cell immunophenotype as CD19-positive;
• Expected survival time exceeding 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• Key organ functions meeting the following criteria: left ventricular ejection fraction ≥50% by echocardiography; serum creatinine ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN; total bilirubin ≤1.5 × ULN;
• Negative pregnancy test for women of childbearing potential; both males and females agree to use effective contraception during treatment and for 1 year thereafter;
• Toxicity from prior anti-tumor therapy ≤ Grade 1 (according to CTCAE v5.0) or at an acceptable level per inclusion/exclusion criteria;
• No significant hereditary diseases;
• Able to comprehend the trial requirements and procedures, and willing to participate in the clinical study as required;
• Signed informed consent form for the trial

Exclusion criteria

• Presence of central nervous system (CNS) involvement or a clinically significant history of CNS diseases, such as epilepsy and cerebrovascular diseases;
• Pregnant or lactating women, or women who disagree to use effective contraception during treatment and within 1 year after treatment;
• Other malignancies that are not in remission;
• Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy;
• Patients who have received allogeneic immune cell therapy within 6 months before enrollment, or donor lymphocyte infusion within 6 weeks before enrollment;
• Confirmed positive anti-FMC63 and DSA responses in the patient's serum;
• Patients who have participated in other clinical trials within 4 weeks before enrollment;
• Uncontrolled infectious diseases or other serious conditions, including but not limited to infections (human immunodeficiency virus, acute or chronic active hepatitis B or C), congestive heart failure, unstable angina, arrhythmia, or conditions considered by the treating physician to pose unpredictable risks;
• History of stroke or intracranial hemorrhage within 3 months before enrollment;
• Major surgery or trauma within 28 days before enrollment, or main side effects not yet recovered;
• History of allergy to any component of the cell product;
• Inability to understand or unwillingness to sign the informed consent form;
• Other reasons deemed by the researchers as unsuitable for the clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The first affiliated hospital of fujian medical university — Fuzhou

Identifiers

NCT: NCT07491263 · QH10309-NHB-01（0）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗