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

Trial Status: Active

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, patient will have assessments performed more frequently in the first month and then 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. Efficacy and safety will be assessed at study visits and as clinically indicated 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.

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: A. 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) E. 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, Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, 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 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 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 9. Treatment with any prior gene or engineered T cell therapy

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
Children's Hospital Los Angeles
Status: ACTIVE
Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
San Diego
Rady Children's Hospital - San Diego
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE
Contact: Helen Diller Family Comprehensive Cancer Center
Phone: 877-827-3222

Colorado

Aurora
Children's Hospital Colorado
Status: APPROVED

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: APPROVED

Indiana

Indianapolis
Riley Hospital for Children
Status: ACTIVE
Contact: Anne Bubnick
Phone: 317-948-0101

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New York

Buffalo
Roswell Park Cancer Institute
Status: APPROVED
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: APPROVED
Columbus
Nationwide Children's Hospital
Status: IN_REVIEW

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Pennsylvania

Philadelphia
Children's Hospital of Philadelphia
Status: ACTIVE
Contact: Laura Motley
Phone: 215-590-2985

South Carolina

Charleston
Medical University of South Carolina
Status: IN_REVIEW

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479

Utah

Salt Lake City
Primary Children's Hospital
Status: ACTIVE

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: ACTIVE

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID CCTL019G2201J
  • Secondary IDs NCI-2019-02353, 2017-002116-14
  • Clinicaltrials.gov ID NCT03876769