Safety, Tolerability, and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy for r/r B-ALL: a Clinical Trial

NCT ID: NCT06326008

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-15
• Study Completion Date: 2026-12-30

Brief Summary

This is an investigator-initiated, single-arm, open-label, non-randomised phase I clinical study. The objective of this trial is to evaluate the safety, tolerability and pharmacokinetics of donor-derived CD19 CAR Therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR Therapy for r/r B-ALL and to explore the efficacy of this therapy preliminarily. The primary endpoints are incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridged allogeneic haematopoietic stem cell transplantation; total number, incidence and severity of adverse events from donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T cell infusion). The secondary endpoints are total number, incidence and severity of adverse events from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion; ORR(CR+CRi) on days 45, 90, 120; duration of response(DOR), event-free survival(EFS), overall survival(OS); pharmacokinetics characteristics. The trial plan to enroll 3~12 cases in dose escalation phase and 36 cases in dose expansion phase.

Conditions

B-cell Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia, in Relapse

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm-1

Participants receive donor-derived CD19 CAR therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR therapy

Group Type: EXPERIMENTAL

Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy

Intervention Type: DRUG

Peripheral blood mononuclear cells for the production of CD19 CAR T cells and CD22 CAR T cells are collected from donors and haematopoietic stem cells are collected from donors.

Interventions

Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy

Peripheral blood mononuclear cells for the production of CD19 CAR T cells and CD22 CAR T cells are collected from donors and haematopoietic stem cells are collected from donors.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with relapsed or refractory CD19+/CD22+ (FCM >95%) B-cell acute lymphoblastic leukaemia who have progressed despite or are intolerant to all standard therapies, including, but not limited to, immunotherapies such as Blinatumomab (BITE), Tyrosine kinase inhibitors (TKI), CAR T-cell therapy, etc.; Currently available therapies have a limited prognosis and there are no available curative treatment options (e.g., HSCT or chemotherapy);

2. Peripheral blood tumour burden ≥60% or severe peripheral blood cytopenia, unsuitable/unable to collect autologous lymphocytes;

3. 1 to 18 years old;

4. Patient's expected survival time ≥ 60 days;

5. Physical status: ECOG score 0-2;

6. Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;

7. Sign an informed consent form during the screening period. Pediatric patients under 8~18 years of age need to have sufficient awareness to voluntarily sign an informed consent form, and their legal representatives (guardians) also need to voluntarily sign an informed consent form; pediatric patients aged 1~7 years can only be recruited after their legal guardians have voluntarily signed an informed consent form.

Exclusion Criteria

• Patients who meet any of the following criteria are not eligible for enrolment.

1. Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);

2. Intracranial hypertension or cerebral impaired consciousness;

3. Symptomatic heart failure or severe cardiac arrhythmia;

4. Symptoms of severe respiratory failure;

5. With other types of malignant tumours;

6. Diffuse intravascular coagulation;

7. Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;

8. Suffering from sepsis or other uncontrollable infections;

9. Suffering from uncontrollable diabetes mellitus;

10. Severe mental disorders;

11. Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);

12. Have organ transplant history;

13. Female patients (patients of childbearing potential) with positive blood HCG test;

14. Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;

15. No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing GoBroad Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jing Pan

Director of Dept of Hemato-Oncology and Immunotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Tengyu Wang

Role: CONTACT

tengyu.wang@gohealtharo.com

86+18333186020

Other Identifiers

BJGBYY-IIT-LCYJ-2023-002

Identifier Type: -

Identifier Source: org_study_id