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

Korábbi kezelés

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

Más betegség

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

Laborértékek

• Bilirubin \>3x upper norma limit
• Creatinine \>3x upper norma limit

Egyéb

• \<50% expression of both CD19 and CD22 on the leukemic population
• Oxygen saturation ≤ 90%
• Active acute GVHD overall grade ≥2 (Seattle criteria)
• Pregnant or lactating women.

• 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)