Bispecific CD19/CD22 CAR-T for Treatment of Children and Young Adults With r/r B-ALL

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to evaluate the safety and efficiency of autologous CD19/CD22 CAR-T lymphocytes in a cohort of pediatric and young adult patients with relapsed /refractory B-lineage acute lymphoblastic leukemia

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Treatments: Cyclophosphamide; Cytarabine; Dexamethasone; Etoposide; Fludarabine

Criteria

Inclusion Criteria:

• Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent

• CD19 or CD22 expression must be detected on greater than 50% of leukemic cells by flow cytometry

• Presence of a measurable mass of tumor cells in the bone marrow or extramedullary sites at the time of patient's inclusion in the study

• Patients with relapsed or refractory CD19 and CD22-expressing B-cell ALL:

• Induction failure

• MRD ≥ 0,1% after 2nd chemotherapy course for high-risk group patients.

• First bone marrow or combined relapse of acute lymphoblastic leukemia, no CR or MRD ≥ 0,1% after 1-course 2nd line therapy

• Second and further relapse of ALL

• Relapse or MRD ≥ 0,1% of ALL after hematopoietic stem cell transplant (> 60 days post alloHSCT)o There must be no available alternative approved curative therapies

• Patient Clinical Performance Status: Karnofsky >50% or Lansky >50%

• Patient Life Expectancy > 4 weeks

• Patients recovered from acute toxic effects of prior chemotherapy, immune- or radiotherapy

• Patient absolute blood naïve (CD45RA+) T-lymphocyte count ≥ 50/mm3

• Patient cardiac function left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.

• Patients who agree to long-term follow up for up to 5 years (if received CD19/CD22 CAR-T cell infusion)

• March 2021 amendment: Healthy HLA-matched related or haploidentical donor (only for HSCT cohort)

Exclusion Criteria:

• <50% expression of both CD19 and CD22 on the leukemic population

• Active (detectable viremia) hepatitis B, C or HIV infection

• Oxygen saturation ≤ 90%

• Bilirubin >3x upper norma limit

• Creatinine >3x upper norma limit

• Active acute GVHD overall grade ≥2 (Seattle criteria)

• Moderate/severe chronic GVHD (NIH consensus) requiring systemic steroids

• Clinical signs of grade > 3 CNS disorders (seizure disorder, paresis, aphasia, cerebrovascular, ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)

• Pregnant or lactating women.

• Active (unresolved) severe infection