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

NCT06326008 | Recruiting Phase 1 DMC

• 1 other identifier: BJGBYY-IIT-LCYJ-2023-002
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  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 bridging allogeneic haematopoietic stem cell transplantation will be recorded.

  Within 43 days of donor-derived CD19 CAR T-cell infusion

• Adverse events (AEs)

  Total number, incidence and severity of adverse events (AEs) from the time of 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) will be recorded.

  Within 120 days of donor-derived CD19 CAR T-cell infusion

Secondary Outcomes (8)

• Long-term Adverse events (AEs)

  From 120 days to 2 years after donor-derived CD19 CAR T-cell infusion

• Objective response rate(ORR)

  day 30, day 45, day 90

• Duration of response (DOR)

  Up to 2 years

• Event-free survival (EFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

Study Arms (1)

Arm-1

EXPERIMENTAL

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

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

Interventions

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

Arm-1

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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);
• Peripheral blood tumour burden ≥60% or severe peripheral blood cytopenia, unsuitable/unable to collect autologous lymphocytes;
• to 18 years old;
• Patient's expected survival time ≥ 60 days;
• Physical status: ECOG score 0-2;
• Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;
• 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.

You may not qualify if:

• Patients who meet any of the following criteria are not eligible for enrolment.
• Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);
• Intracranial hypertension or cerebral impaired consciousness;
• Symptomatic heart failure or severe cardiac arrhythmia;
• Symptoms of severe respiratory failure;
• With other types of malignant tumours;
• Diffuse intravascular coagulation;
• Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
• Suffering from sepsis or other uncontrollable infections;
• Suffering from uncontrollable diabetes mellitus;
• Severe mental disorders;
• Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);
• Have organ transplant history;
• Female patients (patients of childbearing potential) with positive blood HCG test;
• Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;

Sponsors & Collaborators

• Beijing GoBroad Hospital: lead

Study Sites (1)

Beijing GoBroad Hospital

Beijing, Beijing Municipality, 102206, China

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Central Study Contacts

Tengyu Wang

CONTACT

86+18333186020; tengyu.wang@gohealtharo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Dept of Hemato-Oncology and Immunotherapy

Study Record Dates

• First Submitted: March 10, 2024
• First Posted: March 22, 2024
• Study Start: March 15, 2026
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

CN (1)