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

NCT ID: NCT03876769

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-24

Study Completion Date

2027-10-19

Brief Summary

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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.

Detailed Description

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Conditions

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B-Cell Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Single dose of CTL019

Based on the subject's weight one of two possible dose ranges will be prepared for the subject:

Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight

OR

Subjects \> 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells

Group Type EXPERIMENTAL

CTL019

Intervention Type BIOLOGICAL

Based on the subject's weight, one of two possible dose ranges will be prepared for the subject:

Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight

OR

Subjects \> 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells

Interventions

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CTL019

Based on the subject's weight, one of two possible dose ranges will be prepared for the subject:

Subjects ≤ 50 kg: 0.2 to 5.0 x 10(6) CAR-positive viable T cells per kg body weight

OR

Subjects \> 50 kg: 0.1 to 2.5 x 10(8) CAR-positive viable T cells

Intervention Type BIOLOGICAL

Eligibility Criteria

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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 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.
Minimum Eligible Age

1 Year

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Oncology Group

NETWORK

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Children s Hospital of Alabama

Birmingham, Alabama, United States

Site Status

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Site Status

City of Hope National Medical

Duarte, California, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

Mattel Childrens Hospital UCLA

Los Angeles, California, United States

Site Status

Childrens Hospital of Orange County

Orange, California, United States

Site Status

Rady Children s Hospital

San Diego, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Childrens Hospital Colorado

Aurora, Colorado, United States

Site Status

Childrens National Hospital

Washington D.C., District of Columbia, United States

Site Status

Johns Hopkins All Childrens

St. Petersburg, Florida, United States

Site Status

Childrens Healthcare of Atlanta

Atlanta, Georgia, United States

Site Status

James Whitcomb Riley Hospital For Children

Indianapolis, Indiana, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Children s Mercy Hospital

Kansas City, Missouri, United States

Site Status

Hackensack Uni Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cinn Children Hosp Medical Center

Cincinnati, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

The Childrens Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Univ of Texas Southwest Med Center

Dallas, Texas, United States

Site Status

Texas Children's Cancer and Hematology Center

Houston, Texas, United States

Site Status

Methodist Childrens Hospital

San Antonio, Texas, United States

Site Status

University of Utah Clinical Trials Office

Salt Lake City, Utah, United States

Site Status

University of Wisconsin Hospital and Clinics Pharmacy/Drug Shipping Address

Madison, Wisconsin, United States

Site Status

Childrens Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Novartis Investigative Site

Ghent, , Belgium

Site Status

Novartis Investigative Site

Calgary, Alberta, Canada

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Copenhagen, , Denmark

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Roma, RM, Italy

Site Status

Prinses Maxima Centrum voor Kinderoncologie

Utrecht, CS, Netherlands

Site Status

Novartis Investigative Site

Utrecht, , Netherlands

Site Status

Novartis Investigative Site

Oslo, , Norway

Site Status

Novartis Investigative Site

Esplugues, Barcelona, Spain

Site Status

Novartis Investigative Site

Gothenburg, , Sweden

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Countries

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United States Belgium Canada Denmark France Italy Netherlands Norway Spain Sweden United Kingdom

References

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Seftel MD. Hyper-CVAD: a regimen for all seasons. Lancet Haematol. 2020 Jul;7(7):e501-e502. doi: 10.1016/S2352-3026(20)30179-4. No abstract available.

Reference Type DERIVED
PMID: 32589970 (View on PubMed)

Other Identifiers

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2017-002116-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCTL019G2201J

Identifier Type: -

Identifier Source: org_study_id

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