CAR-T Cell Therapy for Blood Cancers: Study MT2017-45

Inclusion Criteria

• Age and Disease Status:
  • For Arm A (Kymriah): Ages 0-25 years
  • For Arm G (Tecartus): Ages over 18 years
  • Must have relapsed or difficult-to-treat pediatric B-cell ALL, defined by:
    • No complete remission after at least 2 cycles of initial chemotherapy
    • Persistent minimal residual disease after at least 2 cycles of consolidation chemotherapy
    • In second or greater relapse of B-ALL
    • Persistent CNS leukemia
    • Down Syndrome or other congenital diseases fitting criteria for second or greater relapse or refractory leukemia
    • Ph+ ALL patients who failed or are intolerant to two lines of TKI
• Performance Status:
  • Arm A: Karnofsky (age ≥16) or Lansky (age <16) performance status ≥ 50%
  • Arm G: ECOG 0, 1, or 2
• Organ Function:
  • Renal function: Serum creatinine ≤1.5 x ULN or eGFR ≥ 50 mL/min/1.73 m²
  • Liver function: ALT ≤ 5 times ULN for age, Bilirubin ≤ 2.0 mg/dl (exceptions for Gilbert syndrome)
  • Pulmonary reserve: ≤ Grade 1 dyspnea, SpO2 > 91% on room air
  • Hemodynamically stable, LVEF ≥ 45%
• Other Criteria:
  • Life expectancy ≥12 weeks
  • Use of adequate birth control for women of childbearing potential and sexually active males
  • Written consent from adults or parental/guardian consent for minors or adults with diminished capacity

Exclusion Criteria

• Pregnant or breastfeeding women
• Patients with Burkitt's lymphoma/leukemia
• CNS 2A
• CAR-T not indicated for primary CNS lymphoma
• Grade 2 to 4 acute or extensive chronic GVHD
• Uncontrolled active hepatitis B or C
• Active HIV infection
• Uncontrolled acute life-threatening infections
• Recent unstable angina or myocardial infarction
• Recent investigational medicinal product use
• Intolerance to CAR-T cell product excipients
• Recent use of immunosuppressive medication

ARM B: Yescarta for Relapsed or Refractory Diffuse Large B Cell Lymphoma

Inclusion Criteria:

• Adult patients (age ≥ 18 years)
• Specific types of lymphoma with CD19 expression
• Chemotherapy refractory disease or relapsed after previous treatments
• Measurable disease at time of apheresis
• ECOG performance status 0-2
• Adequate organ function and bone marrow reserve
• Life expectancy ≥12 weeks
• Use of adequate birth control
• Written consent

Exclusion Criteria:

• Pregnant or breastfeeding women
• Active CNS involvement by malignancy
• Grade 2 to 4 acute or extensive chronic GVHD
• Uncontrolled active hepatitis B or C
• Active HIV infection
• Uncontrolled acute life-threatening infections
• Recent unstable angina or myocardial infarction
• Recent investigational medicinal product use
• Intolerance to CAR-T cell product excipients
• Recent use of immunosuppressive medication

ARM C: Kymriah for Relapsed or Refractory Diffuse Large B Cell Lymphoma

Inclusion Criteria:

• Adult patients (age ≥ 18 years)
• Relapsed or refractory large B-cell lymphoma
• ECOG performance status 0-2
• Adequate organ function and bone marrow reserve
• Life expectancy ≥12 weeks
• Use of adequate birth control
• Written consent

Exclusion Criteria:

• Pregnant or breastfeeding women
• Active CNS involvement by malignancy
• Grade 2 to 4 acute or extensive chronic GVHD
• Uncontrolled active hepatitis B or C
• Active HIV infection
• Uncontrolled acute life-threatening infections
• Recent unstable angina or myocardial infarction
• Recent investigational medicinal product use
• Intolerance to CAR-T cell product excipients
• Recent use of immunosuppressive medication

ARM D: Tecartus for Relapsed or Refractory Mantle Cell Lymphoma

Inclusion Criteria:

• Relapsed or refractory mantle cell lymphoma
• ECOG performance status 0-1
• Adequate organ function and bone marrow reserve
• Life expectancy ≥12 weeks
• Use of adequate birth control
• Written consent

Exclusion Criteria:

• Pregnant or breastfeeding women
• Active CNS involvement by malignancy
• Grade 2 to 4 acute or extensive chronic GVHD
• Uncontrolled active hepatitis B or C
• Active HIV infection
• Uncontrolled acute life-threatening infections
• Recent unstable angina or myocardial infarction
• Recent investigational medicinal product use
• Intolerance to CAR-T cell product excipients
• Recent use of immunosuppressive medication

ARM E: Breyanzi for Relapsed or Refractory Large B-Cell Lymphoma

Inclusion Criteria:

• Adult patients (age ≥ 18 years)
• Relapsed or refractory disease after two or more lines of therapy
• ECOG performance status 0-2
• Adequate organ function and bone marrow reserve
• Life expectancy ≥12 weeks
• Use of adequate birth control
• Written consent

Exclusion Criteria:

• Pregnant or breastfeeding women
• Active CNS involvement by malignancy
• Grade 2 to 4 acute or extensive chronic GVHD
• Uncontrolled active hepatitis B or C
• Active HIV infection
• Uncontrolled acute life-threatening infections
• Recent unstable angina or myocardial infarction
• Recent investigational medicinal product use
• Intolerance to CAR-T cell product excipients
• Recent use of immunosuppressive medication

ARM F: Abecma for Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

• Adult patients (age ≥ 18 years)
• Relapsed or refractory multiple myeloma
• ECOG performance status 0-1
• Adequate organ function and bone marrow reserve
• Life expectancy ≥12 weeks
• Use of adequate birth control
• Written consent

Exclusion Criteria:

• Pregnant or breastfeeding women
• Active CNS involvement by malignancy
• Grade 2 to 4 acute or extensive chronic GVHD
• Uncontrolled active hepatitis B or C
• Active HIV infection
• Uncontrolled acute life-threatening infections
• Recent unstable angina or myocardial infarction
• Recent investigational medicinal product use
• Intolerance to CAR-T cell product excipients
• Recent use of immunosuppressive medication