Donor-derived CD19 CAR T cells with allo‑HSCT followed by donor-derived CD22 CAR T cells for relapsed/refractory B‑ALL

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

This study tests donor-derived CD19 CAR T cells followed by an allogeneic stem‑cell transplant and sequential donor-derived CD22 CAR T cells in children and adolescents (1–18 years) with relapsed or refractory CD19+/CD22+ B‑ALL who cannot provide their own cells.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 1 Year to 18 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (Academic / other)
• Drugs / interventions: Blinatumomab, CAR T, chemotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06326008 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open‑label phase I trial that gives donor-derived CD19 CAR T cells, then an allogeneic hematopoietic stem‑cell transplant (allo‑HSCT), and later donor-derived CD22 CAR T cells to patients with relapsed/refractory CD19+/CD22+ B‑ALL. The primary focus is safety, tolerability, and pharmacokinetics, with dose‑limiting toxicities monitored in the first 28 days after the CD19 CAR infusion and adverse events tracked through 120 days and up to two years. Eligible patients are aged 1–18 with high peripheral blood tumor burden or severe cytopenia preventing autologous lymphocyte collection and must have a DSA‑negative HLA‑identical or haploidentical donor. Secondary outcomes include preliminary measures of efficacy such as overall response rate.

Who should consider this trial

Good fit: Children and adolescents (1–18 years) with relapsed or refractory CD19+/CD22+ B‑ALL, peripheral blood tumor burden ≥60% or severe cytopenia preventing autologous collection, expected survival ≥60 days, ECOG 0–2, and an available DSA‑negative HLA‑identical or haploidentical donor are ideal candidates.

Not a fit: Patients without CD19 or CD22 expression, adults older than 18, those without an eligible donor, those with very limited life expectancy, or those with comorbidities that preclude transplantation or CAR‑T therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could provide a new option to induce remission in children and adolescents with refractory CD19+/CD22+ B‑ALL who lack usable autologous cells.

How similar studies have performed: Autologous CD19 CAR‑T and CD22‑targeted CAR‑T therapies have produced remissions and sequential targeting after CD19 relapse has shown promise, but donor‑derived CAR‑T bridged with allo‑HSCT is less established and remains experimental.

Eligibility criteria

Inclusion Criteria:

\- Patients will be enrolled only if they meet all the 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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing GoBroad Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Tengyu Wang

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