Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients
Condition: B-cell Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: CTL019
Intervention description: Tisagenlecleucel was administered as a single iv infusion. Dose: 2.0 to 5.0x10^6 tisagenlecleucel per kg body weight (for patients ≤ 50 kg) or 1.0 to 2.5x10^8 tisagenlecleucel (for patients >50 kg).
Intervention MeSH terms: Tisagenlecleucel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Maximum age: 25 Years
Healthy volunteers: No
Keywords: Pediatric; ALL; Cell therapy; Lymphoblastic Leukemia; Acute; High Risk; Childhood; CTL019; tisagenlecleucel; Pediatric patients; r/r B-cell ALL; high risk B-cell ALL at first relapse; high risk B-cell ALL that relapsed < 6 months post allo-HSCT

Summary:

      This is a single arm, open-label, multi-center, phase II study to determine the efficacy and
      safety of CTL019 in pediatric patients with r/r B-cell ALL.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Relapsed or refractory pediatric B-cell ALL

          2. Adequate organ function

          3. For relapsed patients, documentation of CD19 tumor expression within 3 months of study
             entry.

          4. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.

          5. Life expectancy > 12 weeks.

          6. Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50 at
             screening

          7. Signed written informed consent and assent forms

          8. Must meet the institutional criteria to undergo leukapheresis or have an acceptable,
             store leukapheresis product

          9. Must have an apheresis product of non-mobilized cells received and accepted by the
             manufacturing site.

         10. Cohort 1 only:

               1. First relapse AND hypodiploid cytogenetics OR

               2. First relapse AND t(17;19) with defined TCF3-HLF fusion OR

               3. First relapse with any cytogenetics provided the relapse occurred ≤ 36 months of
                  initial diagnosis AND MRD at end of reinduction therapy is ≥0.01% by flow
                  cytometry (local assessment)

        Exclusion Criteria

          1. Isolated extra-medullary disease relapse

          2. Patients with concomitant genetic syndrome: such as patients with Fanconi anemia,
             Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome.
             Patients with Down Syndrome will not be excluded.

          3. Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL,
             leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL,
             with FAB L3 morphology and /or a MYC translocation)

          4. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
             intent and with no evidence of active disease

          5. Treatment with any prior gene therapy product

          6. Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19
             therapy

          7. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening),
             or any uncontrolled infection at screening

          8. Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening

          9. Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).

         10. Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.

         11. Patient has an investigational medicinal product within the last 30 days prior to
             screening.

         12. Pregnant or nursing (lactating) women.

         13. Women of child-bearing potential, defined as physiologically capable of becoming
             pregnant, unless they agree to use highly effective methods of contraception for at
             least 12 months after the CTL019 infusion and after CAR T-cells are no longer present
             by qPCR on two consecutive tests

         14. Sexually active males must use a condom during intercourse at least 12 months after
             the CTL019 infusion after CAR T-cells are no longer present by qPCR on two consecutive
             tests