Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (CASSIOPEIA)

Why are we doing this research?

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who received first-line treatment and are EOC MRD positive. The study will have the following sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After tisagenlecleucel infusion, efficacy will be assessed at Day 29, then every 3 months for the first year, every 6 months for the second year, then yearly until the end of the study. Safety will be assessed throughout the study. The study is expected to end in approximately 8 years after first patient first treatment (FPFT). A post-study long term follow-up for lentiviral vector safety will continue under a separate protocol per health authority guidelines.

CCTL019G2201J:  A Phase II Trial of Tisagenlecleucel in First-line High-risk (HR) Pediatric and Young Adult Patients With B-cell Acute Lymphoblastic Leukemia (B-ALL) Who Are Minimal Residual Disease (MRD) Positive at the End of Consolidation (EOC) Therapy

Who can participate?

Inclusion Criteria:

  • CD19 expressing B-cell Acute Lymphoblastic Leukemia
  • De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
  • Age 1 to 25 years at the time of screening
  • Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
  • Adequate organ function during the screening period:
    • Renal function based on age/gender
    • ALT ≤ 5 times ULN for age
    • AST ≤ 5 times ULN for age
    • Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL)
    • Adequate pulmonary function defined as:
      • no or mild dyspnea (≤ Grade 1)
      • oxygen saturation of > 90% on room air F. Adequate cardiac function defined as LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
  • Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, augmented Berlin-Frankfurt-Münster (BFM) consolidation, and interim maintenance with high-dose methotrexate.

Exclusion Criteria:

  • M3 marrow at the completion of 1st line induction therapy
  • M2 or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of enrollment.
  • Philadelphia chromosome positive ALL
  • Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
  • Prior tyrosine kinase inhibitor therapy
  • Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
  • Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
  • Has had treatment with any prior anti-CD19 therapy. Treatment with any prior gene or engineered T cell therapy

Ages

  • 1 Year to 25 Years  

Conditions

  • Leukemia AML Relapse
  • Adult - Leukemia AML Relapse

Contact

Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org