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
Safety, Tolerability and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allogeneic Haematopoietic Stem Cell Transplantation and Sequential Donor-derived CD22 CAR Therapy in Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia: a Clinical Trial
Beijing GoBroad Hospital
48 participants
Mar 15, 2026
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria7
- 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.
Exclusion Criteria16
- 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;
- No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.
Interventions
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.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06326008