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

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

ClinicalTrials.gov Identifier: NCT03876769

Novartis Reference Number: CCTL019G2201J

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
B-Cell Acute Lymphoblastic Leukemia
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
140 participants
Start date 
Feb 05, 2019
Completion date 
Aug 19, 2027
Gender 
All
Age(s)
1 Years - 25 Years (Child, Adult)

Interventions

Biological
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

Eligibility Criteria

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

Other protocol-defined inclusion/exclusion may apply.

Study Locations

United States
Phoenix Children's Hospital
Recruiting
Phoenix, 85016
Arizona
United States
City of Hope National Medical Center
Recruiting
Duarte, 91010
California
United States
Childrens Hospital Los Angeles SC CTL019
Recruiting
Los Angeles, 90027
California
United States
Mattel Childrens Hospital UCLA
Recruiting
Los Angeles, 90095
California
United States
Rady Children s Hospital CTBM100C2401
Recruiting
San Diego, 92123
California
United States
UCSF Medical Center
Recruiting
San Francisco, 94143
California
United States
Stanford Universtiy Medical Center
Recruiting
Stanford, 94304
California
United States
Childrens Hospital Colorado
Recruiting
Aurora, 80045
Colorado
United States
Children s National Hospital
Recruiting
Washington, 20010
District of Columbia
United States
Johns Hopkins All childrens
Recruiting
Saint Petersburg, 33701
Florida
United States
Children's Healthcare of Atlanta Emory University IRB
Recruiting
Atlanta, 30342
Georgia
United States
James Whitcomb Riley Hospital for Children
Recruiting
Indianapolis, 46202
Indiana
United States
Johns Hopkins Oncology Center Cancer Research Building
Recruiting
Baltimore, 21231
Maryland
United States
Children s Mercy Hospital
Recruiting
Kansas City, 64108
Missouri
United States
Washington University CTBM100C2412
Recruiting
Saint Louis, 63110
Missouri
United States
Hackensack University Medical Center
Recruiting
Hackensack, 07601
New Jersey
United States
Memorial Sloan Kettering Cancer Center
Recruiting
New York, 10065
New York
United States
Duke University Medical Center
Recruiting
Durham, 27710
North Carolina
United States
Cincinnati Children s Hospital Medical Center
Recruiting
Cincinnati, 45229-3039
Ohio
United States
Oregon Health and Science University
Recruiting
Portland, 97239-3098
Oregon
United States
The Childrens Hospital of Philadelphia Div Gastroint., Hepat. & Nutr.
Recruiting
Philadelphia, 19104
Pennsylvania
United States
Monroe Carell Jr Childrens Hospital at Vanderbilt
Recruiting
Nashville, 37232
Tennessee
United States
University of Texas Southwestern Medical Center
Recruiting
Dallas, 75390-9034
Texas
United States
Methodist Children's Hospital
Recruiting
San Antonio, 78229
Texas
United States
University of Utah Clinical Trials Office
Recruiting
Salt Lake City, 84108
Utah
United States
University of Wisconsin Hospital and Clinics Pharmacy/Drug Shipping Address
Recruiting
Madison, 53792
Wisconsin
United States
Belgium
Novartis Investigative Site
Recruiting
Gent, 9000
-
Belgium
Canada
Novartis Investigative Site
Recruiting
Toronto, M5G 1X8
Ontario
Canada
Novartis Investigative Site
Recruiting
Montreal, H3T 1C5
Quebec
Canada
Denmark
Novartis Investigative Site
Recruiting
Copenhagen, 2100
-
Denmark
Finland
Novartis Investigative Site
Recruiting
Helsinki, 00029
-
Finland
France
Novartis Investigative Site
Recruiting
Paris Cedex 19, 75935
-
France
Germany
Novartis Investigative Site
Recruiting
Frankfurt, 60590
-
Germany
Novartis Investigative Site
Recruiting
Muenchen, 81377
-
Germany
Italy
Novartis Investigative Site
Recruiting
Roma, 00165
ITA
Italy
Netherlands
Prinses Maxima Centrum voor Kinderoncologie
Recruiting
Utrecht, 3584
CS
Netherlands
Norway
Novartis Investigative Site
Recruiting
Oslo, 0424
-
Norway
Spain
Novartis Investigative Site
Recruiting
Esplugues de Llobregat, 08950
Barcelona
Spain
United Kingdom
Novartis Investigative Site
Recruiting
London, WC1E 6HX
-
United Kingdom
Novartis Investigative Site
Recruiting
London, WC1N 3JH
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]