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

a study on Acute Lymphoblastic Leukemia Leukemia

Summary

for people ages 1-25 (full criteria)
at San Francisco, California and other locations
study started
estimated completion

Description

Summary

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.

Official 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

Keywords

B-Cell Acute Lymphoblastic Leukemia CTL019 Kymriah ALL tisagenlecleucel HR B-ALL EOC MRD Minimal Residual Disease (MRD) Positive at the End of Consolidation (EOC) Burkitt Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Single dose of CTL019

Eligibility

You can join if…

Open to people ages 1-25

  1. CD19 expressing B-cell Acute Lymphoblastic Leukemia
  2. 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.
  3. Age 1 to 25 years at the time of screening
  4. Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
  5. Adequate organ function during the screening period:
  6. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL)
  7. Adequate pulmonary function defined as:
  8. no or mild dyspnea (≤ Grade 1)
  9. 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
  10. 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.

You CAN'T join if...

  1. M3 marrow at the completion of 1st line induction therapy
  2. 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.
  3. Philadelphia chromosome positive ALL
  4. Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
  5. Prior tyrosine kinase inhibitor therapy
  6. 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.
  7. 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)
  8. Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or engineered T cell therapy

Other protocol-defined inclusion/exclusion may apply.

Locations

  • UCSF Medical Center accepting new patients
    San Francisco California 94143 United States
  • Stanford Universtiy Medical Center accepting new patients
    Stanford California 94304 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT03876769
Phase
Phase 2
Study Type
Interventional
Last Updated