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Protocol No. UW19048

Principal Investigator Capitini, Christian

Phase II

Age Group Both

Scope National

Sponsor Type Industry

Title 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, AALL1721

Objective The purpose of the study is to test an experimental approach called modified T cell therapy for patients with high-risk Acute Lymphoblastic Leukemia (ALL), a type of blood cancer that involves cells in your blood called B cells. Patients are considered high risk based on their age and white blood cell (WBC) (a type of cells that fight infection and other disease) count at the time when they were initially diagnosed with this cancer. This is a study for people who have been found to have this cancer and have received initial therapy (called induction therapy) followed by follow-up therapy (called consolidation therapy) but were still found to have residual (leftover) disease after completing the follow-up therapy

Treatment In this study, T cells (another type of white blood cell) will be removed from your blood (by a procedure called leukapheresis procedure) and changed in a way that will allow them to identify and kill your tumor cells. The modification is done by gene transfer and results in a genetic change to your T cells. This allows the changed T cells to recognize your B-cells (tumor cells but also normal antibody-producing B cells). These changed cells are called tisagenlecleucel cells. If you agree to join in this study, you will get one dose of the tisagenlecleucel cells administered by intravenous infusion. Under certain conditions (that your study doctor will explain to you), after receiving an initial dose of tisagenlecleucel cells, you may be eligible to receive a 2nd dose of tisagenlecleucel cells

Description 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

Key Eligibility
  • CD19 expressing (in peripheral blood or bone marrow by flow cytometry) B-cell Acute Lymphoblastic Leukemia
  • De novo NCI HR B-ALL who received first-line treatment and are MRD greater than or equal to 0.01% at EOC (HR defined by NCI criteria at the time of initial leukemia presentation as age greater than or equal to 10 and/or WBC greater than or equal to 50 x 109 cells/L). 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 less than 16 years) or Karnofsky (age greater than or equal 16 years) performance status greater than or equal 60% at screening
  • Adequate organ function as defined by the protocol
  • Prior induction and consolidation chemotherapy allowed as defined by the protocol
  • Must meet the institutional criteria to undergo leukapheresis
  • Once all other eligibility criteria are confirmed, must have a leukapheresis product of nonmobilized cells received and accepted by the manufacturing site
    EXCLUSION
  • M3 marrow (greater than or equal to 25% blasts by morphologic criteria) at the completion of first-line induction therapy
  • M2 (i.e. greater than or equal to 5% blasts by morphologic criteria) or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy or evidence of disease progression in the peripheral blood or new extramedullary disease prior to enrollment. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of screening
  • Philadelphia chromosome positive (Ph+) ALL
  • Hypodiploid: less than 44 chromosomes and/or DNA index less than 0.81, or other clear evidence of a hypodiploid clone
  • Prior tyrosine kinase inhibitor therapy
  • 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
  • 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
  • Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests
  • Presence of active hepatitis B or C
  • Human Immunodeficiency Virus (HIV) positivity as indicated by serology
  • Can not be pregnant or breastfeeding
  • Male and Female of childbearing potential must agree to adequate birth control as defined by the protocol
  • If subjects are taking any of the following medications, their infusion (including a second infusion) must be delayed until the medications have been stopped according to the following:
  • Medications to be stopped greater than 72 hours prior to tisagenlecleucel infusion: Therapeutic systemic doses of steroids. However, the following physiological replacement doses of steroids are allowed: less than 12 mg/m2/day hydrocortisone or equivalent
  • Medications to be stopped at least 1 week prior to tisagenlecleucel infusion: 6-thioguanine, asparaginase (non-pegylated), vincristine, 6-mercaptopurine, and intrathecal methotrexate
  • Medications to be stopped at least 2 weeks prior to tisagenlecleucel infusion: Anthracyclines and cytarabine, Intravenous methotrexate. Radiotherapy: Non-CNS site of radiation, Pegylated-asparaginase
  • Medications/Therapy to be stopped at least 8 weeks prior to tisagenlecleucel infusion: Radiotherapy: Cranial radiation (for CNS 3 subjects) therapy

  • Applicable Disease Sites Leukemia

    Status Open

    Participating Institutions UW Hospital and Clinics