Clinical trial NCT06056752: QH103 Cell Injection for the Treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
Official title: A Dose-escalation Clinical Study of QH103 Cell Injection (CD19 CAR-γδT Cell Injection) in Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-cell Acute Lymphoblastic Leukemia
Keywords: B-ALL
Allogenic CAR-γδT Cell
CD19
cell therapy
Lead sponsor: Anhui Provincial Hospital
Sponsor class: OTHER_GOV
First posted: 2023-09-28
Enrollment: 10
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, single-center, interventional, dose-escalation clinical study designed to evaluate the safety and tolerability of QH103 Cell Injection in the treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia.

Detailed description: To evaluate the safety and tolerability of QH103 Cell Injection in the treatment of relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia, and to evaluate dose-limiting toxicity and maximum tolerated dose.

Eligibility criteria: Inclusion Criteria:

1. Age ≥14 years, gender is not limited;
2. Patients with clinically diagnosed relapsed/refractory B-ALL (except those presenting with extramedullary disease only), including any of the following:

   1. Failure to obtain CR after 2 cycles of standard chemotherapy;
   2. First induction of CR, but duration of CR is ≤12 months;
   3. Relapsed/refractory B-ALL that has failed to respond to the first or multiple salvage treatments;
   4. Relapse after hematopoietic stem cell transplantation, including hematological relapse and positive micro residual disease (MRD).
3. Cytological or histological confirmation of tumor cell immunophenotyping as CD19 positive;
4. Bone marrow with a ratio of ≥5% primitive/naïve lymphocytes (morphology);
5. Expected survival time of more than 3 months;
6. Eastern Cooperative Oncology Group (ECOG) score of 0-2;
7. Vital organ function meets the following requirements: left ventricular ejection fraction ≥50% on echocardiography; serum creatinine≤1.5 × upper limit of normal range (ULN); glutamine aminotransferase, aspartate aminotransferase ≤3 times ULN, total bilirubin ≤1.5 times ULN;
8. Pregnancy tests for women of childbearing age should be negative, and both men and women should agree to use effective contraception during treatment and for the following 1 year.
9. Toxicity of prior antitumor therapy ≤ grade 1 (according to CTCAE version 5.0) or acceptable inclusion/exclusion criteria level.
10. No significant hereditary disease;
11. Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;
12. Sign the trial informed consent form.

Exclusion Criteria:

1. with uncontrolled active central nervous system leukemia (CNSL) or a history of epilepsy, cerebrovascular disease
2. Pregnant or lactating women, or those who do not consent to the use of the drug during and within 1 year after treatment;
3. Other malignant tumors not in remission;
4. with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy;
5. Patients who have received immune cell therapy within 6 months prior to enrollment and donor lymphocyte infusion within 6 weeks prior to enrollment.
6. Patients with confirmed positive serum anti-FMC63 and DSA reactions;
7. Patients who have participated in other clinical trials within 4 weeks prior to enrollment;
8. Uncontrolled infectious or other serious diseases, including but not limited to infections (Human Immunodeficiency Virus, acute or chronic active hepatitis B or hepatitis C), congestive heart failure, unstable angina pectoris cardiac arrhythmias, or conditions that the attending physician considers to be an unpredictable risk;
9. Uncontrollable plasma fluid, such as large pleural effusions or ascites;
10. History of stroke or intracranial hemorrhage within 3 months prior to enrollment;
11. Major surgery or trauma within 28 days prior to enrollment, or major side effects from which you have not recovered;
12. History of allergy to any of the ingredients in the cellular product;
13. Inability to understand or unwillingness to sign the informed consent form;
14. Other reasons deemed by the investigator to be unsuitable for the clinical trial.

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: 12 months
measure: Incidence of Dose-Limiting Toxicities (DLTs)
timeFrame: First infusion date of QH103 cells to 28 days end cell infusion
measure: Maximum tolerated dose (MTD)
timeFrame: 28 days
Secondary outcomes:
measure: Overall Survival (OS）
timeFrame: 12 months
measure: Progression Free Survival (PFS)
timeFrame: 12 months
measure: Pharmacokinetics: Persistence of the QH103 cells
timeFrame: 28 days
measure: Pharmacodynamics: Peak level of cytokines in serum
timeFrame: 28 days
measure: Overall Response Rate(ORR)
timeFrame: 12 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
Study officials:
affiliation: Director of Hematology Department, Anhui Provincial Hospital
name: Xiaoyu Zhu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: