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This Phase 1/2 study evaluates the safety and efficacy of autologous CD19/CD22 CAR-T lymphocytes in children and young adults with relapsed or refractory B-lineage acute lymphoblastic leukemia. The treatment plan also includes agents such as fludarabine, cyclophosphamide, cytarabine, etoposide, dexamethasone, tocilizumab and allogeneic HSCT. To take part, CD19 or CD22 expression must be detected by flow cytometry on more than 50% of leukemic cells and a measurable tumor mass must be present; informed consent is given by the patient over 14 and by a legal guardian for those under 18.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
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