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


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Trial ID: NCT03876769


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 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

Stanford Investigator(s)


Inclusion Criteria:

   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:

   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

   6. 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:

   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 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.

   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

   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.


biological: CTL019


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Michelle Fujimoto

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