QH103 Cell Injection for the Treatment of Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

NCT06056752 | Recruiting Phase 1

• 1 other identifier: QH10302-B-01(0)
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

B-ALL; Allogenic CAR-γδT Cell; CD19; cell therapy

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events (AEs)

  AE is defined as any adverse medical event from the date of leukapheresis to 12 months after QH103 infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0

  12 months

• Incidence of Dose-Limiting Toxicities (DLTs)

  DLT was defined as QH103 Cells-related events with onset within first 28 days following infusion: The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting \> 2 weeks; Any QH103 cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.

  First infusion date of QH103 cells to 28 days end cell infusion

• Maximum tolerated dose (MTD)

  MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.

  28 days

Secondary Outcomes (5)

• Overall Survival (OS）

  12 months

• Progression Free Survival (PFS)

  12 months

• Pharmacokinetics: Persistence of the QH103 cells

  28 days

• Pharmacodynamics: Peak level of cytokines in serum

  28 days

• Overall Response Rate(ORR)

  12 months

Study Arms (1)

Patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia

EXPERIMENTAL

A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells

Biological: QH103 Cell Injection; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

QH103 Cell Injection BIOLOGICAL

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

Patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia

Fludarabine DRUG

Intravenous fludarabine on days-5\~-2,the infusion dose is adjusted according to the subject's condition

Also known as: Fludarabine Phosphate for Injection

Patients with relapsed/refractory CD19-positive B-cell acute lymphoblastic leukemia

Cyclophosphamide DRUG

Intravenous cyclophosphamide on days -5\~-3, the infusion dose is adjusted according to the subject's condition

Also known as: Cyclophosphamide for Injection

Patients with relapsed/refractory CD19-positive 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 is not limited;
• Patients with clinically diagnosed relapsed/refractory B-ALL (except those presenting with extramedullary disease only), including any of the following:
• Failure to obtain CR after 2 cycles of standard chemotherapy;
• First induction of CR, but duration of CR is ≤12 months;
• Relapsed/refractory B-ALL that has failed to respond to the first or multiple salvage treatments;
• Relapse after hematopoietic stem cell transplantation, including hematological relapse and positive micro residual disease (MRD).
• Cytological or histological confirmation of tumor cell immunophenotyping as CD19 positive;
• Bone marrow with a ratio of ≥5% primitive/naïve lymphocytes (morphology);
• Expected survival time of more than 3 months;
• Eastern Cooperative Oncology Group (ECOG) score of 0-2;
• 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;
• 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.

You may not qualify if:

• No significant hereditary disease;
• Be able to understand the requirements and matters of the trial and be willing to participate in the clinical study as required;
• Sign the trial informed consent form.
• with uncontrolled active central nervous system leukemia (CNSL) or a history of epilepsy, cerebrovascular disease
• Pregnant or lactating women, or those who do not consent to the use of the drug during and within 1 year after treatment;
• Other malignant tumors not in remission;
• with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy;
• Patients who have received immune cell therapy within 6 months prior to enrollment and donor lymphocyte infusion within 6 weeks prior to enrollment.
• Patients with confirmed positive serum anti-FMC63 and DSA reactions;
• Patients who have participated in other clinical trials within 4 weeks prior to enrollment;
• 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;
• Uncontrollable plasma fluid, such as large pleural effusions or ascites;
• History of stroke or intracranial hemorrhage within 3 months prior to enrollment;
• Major surgery or trauma within 28 days prior to enrollment, or major side effects from which you have not recovered;
• History of allergy to any of the ingredients in the cellular product;

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

Study Sites (1)

Anhui Provincial Hospital

Hefei, Anhui, 230036, China

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

fludarabine; fludarabine phosphate; Injections; 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)

Drug Administration Routes; Drug Therapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Xiaoyu Zhu, Ph.D

  Director of Hematology Department, Anhui Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoyu Zhu, Ph.D

CONTACT

+86 15255456091; xiaoyuz@ustc.edu.cn

Guangyu Sun

CONTACT

+86 13956970687; sunguangyu_vip@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology Department

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: September 28, 2023
• Study Start: September 27, 2023
• Primary Completion: July 3, 2025
• Study Completion (Estimated): July 3, 2026
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

CN (1)