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

Last Update: May 24, 2022

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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
Start date 
Jun 24, 2019
Completion date 
Jun 28, 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
Children s Hospital of Alabama
Recruiting
Birmingham, 35233 - Alabama
Contact: Melissa Wallace - [email protected] - Matthew Kutny
United States
Phoenix Children's Hospital
Recruiting
Phoenix, 85016 - Arizona
Contact: Dresden Whitehead (602-546-0985) - [email protected] - Dana Salzberg
United States
City of Hope National Medical Center
Recruiting
Duarte, 91010 - California
Contact: (+1 626 256 4673 Ext 85013) Anna Pawlowska
United States
Childrens Hospital Los Angeles SC CTL019
Recruiting
Los Angeles, 90027 - California
Contact: Lee Chen (323-361-8670) - [email protected] - Emily Hsieh
United States
Mattel Childrens Hospital UCLA
Recruiting
Los Angeles, 90095 - California
Contact: Eunice Kim - [email protected] - William May
United States
Children's Hospital of Orange County CHOC Children's
Recruiting
Orange, 92868-3874 - California
Contact: Lissamarie Donjuan - [email protected] - Van Huynh
United States
Rady Children s Hospital CTBM100C2401
Recruiting
San Diego, 92123 - California
Contact: Sheila Medina-Torne (858-966-8153) - [email protected] - Deborah Schiff
United States
UCSF Medical Center
Recruiting
San Francisco, 94143 - California
Contact: Emily Theobald (415-353-1351) - [email protected] - Michelle Hermiston
United States
Stanford Universtiy Medical Center
Recruiting
Stanford, 94304 - California
Contact: Amy Li (650-723-4000) - [email protected] - Kara Davis
United States
Childrens Hospital Colorado
Recruiting
Aurora, 80045 - Colorado
Contact: Kelly Losekamp (720-777-5379) - [email protected] - Kelly Maloney
United States
Yale School of Medicine
Recruiting
New Haven, 06519 - Connecticut
Contact: Niketa Shah
United States
Childrens National Hospital
Recruiting
Washington, 20010 - District of Columbia
Contact: Suzie Goodick (202-476-5000) - [email protected] - Anne L Angiolillo
United States
Johns Hopkins All childrens
Recruiting
Saint Petersburg, 33701 - Florida
Contact: Ashley Repp - [email protected] - Benjamin Oshrine
United States
Children's Healthcare of Atlanta Emory University IRB
Recruiting
Atlanta, 30342 - Georgia
Contact: Sarah Votaw - [email protected] - Muna Qayed
United States
Ann and Robert H Lurie Childrens Hospital of Chicago
Recruiting
Chicago, 60611 - Illinois
Contact: Monica Newmark (312-227-4811) - [email protected] - Sonali Chaudhury
United States
University of Chicago
Recruiting
Chicago, 60637 - Illinois
Contact: James Labelle
United States
James Whitcomb Riley Hospital for Children
Recruiting
Indianapolis, 46202 - Indiana
Contact: Jennifer Pencek (317-274-4281) - [email protected] - Jodi Skiles
United States
Johns Hopkins Oncology Center Cancer Research Building
Recruiting
Baltimore, 21231 - Maryland
Contact: Genevieve Courpas (410-502-5940) - [email protected] - Patrick Brown
United States
Dana Farber Cancer Institute Dept.of DFCI
Recruiting
Boston, 02215 - Massachusetts
Contact: Sara Alvarez - [email protected] - Andrew Place
United States
University of Michigan
Recruiting
Ann Arbor, 48109-2800 - Michigan
Contact: Dustin Walling (734-936-8538) - [email protected] - Rajen Mody
United States
University of Minnesota CAEB071B2201
Recruiting
Minneapolis, 55455 - Minnesota
Contact: Mollie Koppes (612-273-6212) - [email protected] - Peter Gordon
United States
Children s Mercy Hospital
Recruiting
Kansas City, 64108 - Missouri
Contact: Robin Ryan (816-234-3977) - [email protected] - Gary D. Myers
United States
St. Louis University/Cardinal Glennon Children's Hospital
Recruiting
Saint Louis, 63104 - Missouri
Contact: Donna Marin (314-577-5608) - [email protected] - William Ferguson
United States
Washington University CTBM100C2412
Recruiting
Saint Louis, 63110 - Missouri
Contact: Amy Monahan (314-454-2253) - [email protected] - Sima Bhatt
United States
University of Nebraska Medical Center
Recruiting
Omaha, 68198 - Nebraska
Contact: Lucy Chung (402-559-4000) - [email protected] - Don Coulter
United States
Hackensack University Medical Center
Recruiting
Hackensack, 07601 - New Jersey
Contact: Hagop Jack Boyajian (+1 201 996 2000) - [email protected] - Alfred Gillio
United States
Roswell Park Cancer Institute
Recruiting
Buffalo, 14263 - New York
Contact: Danielle Schechter (716-845-4485) - [email protected] - Clare Twist
United States
Cohen Children's Medical Center of New York
Recruiting
New Hyde Park, 11040 - New York
Contact: Jessica Stiles (718-470-3493) - [email protected] - Karen Bride
United States
Memorial Sloan Kettering Cancer Center
Recruiting
New York, 10065 - New York
Contact: Maria Paes Pena (212-639-3112) - [email protected] - Kevin Curran
United States
Columbia University Medical Center Oncology
Recruiting
New York, 110032 - New York
Contact: Chez Brivett - [email protected] - Justin Kahn
United States
Duke University Medical Center
Recruiting
Durham, 27710 - North Carolina
Contact: Eileen Phifer (919-681-6898) - [email protected] - Timothy A Driscoll
United States
Cincinnati Children s Hospital Medical Center
Recruiting
Cincinnati, 45229-3039 - Ohio
Contact: Adam Nelson (800-344-2462) - [email protected] - Christine Phillips
United States
Univ Hospital - Cleveland/Rainbow Babies and Children's Hosp Pediatric Nephrology
Recruiting
Cleveland, 44106 - Ohio
Contact: Antoinette Hillian (218-844-3681) - [email protected] - Duncan Stearns
United States
Cleveland Clinic
Recruiting
Cleveland, 44195 - Ohio
Contact: Sarah Housour (216-442-5232) - [email protected] - Rabi Hanna
United States
Nationwide Childrens Hospital suite T6B
Recruiting
Columbus, 43205 - Ohio
Contact: Emily Clark (614-722-2556) - [email protected] - Mark Ranalli
United States
Oregon Health and Science University
Recruiting
Portland, 97239-3098 - Oregon
Contact: Nycole Ferguson (503-494-5893) - [email protected] - Bill Chang
United States
Penn State Childrens Hospital
Recruiting
Hershey, 17033 - Pennsylvania
Contact: Christinia Crnjar (717-531-6955) - [email protected] - Robert Greiner
United States
The Childrens Hospital of Philadelphia Div Gastroint., Hepat. & Nutr.
Recruiting
Philadelphia, 19104 - Pennsylvania
Contact: Anna S. Sparrow (215-590-2985) - [email protected] - Shannon Maude
United States
Medical University of South Carolina Medical Univ of SC
Recruiting
Charleston, 29425 - South Carolina
Contact: Matt Smith (843-876-8614) - [email protected] - Michelle Hudspeth
United States
Monroe Carell Jr Childrens Hospital at Vanderbilt
Recruiting
Nashville, 37232 - Tennessee
Contact: Eugenia Owens (615-321-5247) - [email protected] - Carrie Kitko
United States
University of Texas Southwestern Medical Center
Recruiting
Dallas, 75390-9034 - Texas
Contact: Mariah Black (214-648-1390) - [email protected] - Samuel John
United States
Texas Children's Cancer and Hematology Center
Recruiting
Houston, 77030 - Texas
Contact: Diana Montesinos (832-824-1000) - [email protected] - Rayne Rouce
United States
Methodist Children's Hospital
Recruiting
San Antonio, 78229 - Texas
Contact: Candace Taylor - [email protected] - Lisa Madden
United States
University of Utah Clinical Trials Office
Recruiting
Salt Lake City, 84108 - Utah
Contact: Genesis Arko (801-587-5711) - [email protected] - Luke Maese
United States
Children's Hospital of Richmond at VCU Pediatric Hematology Oncology
Recruiting
Richmond, 23219 - Virginia
Contact: Grace Garren (804-828-9605) - [email protected] - Joseph Laver
United States
University of Wisconsin Hospital and Clinics Pharmacy/Drug Shipping Address
Recruiting
Madison, 53792 - Wisconsin
Contact: Jenny Weiland - [email protected] - Christian Capitini
United States
Childrens Hospital of Wisconsin
Recruiting
Milwaukee, 53226 - Wisconsin
Contact: Isabella Puls - [email protected] - Julie-An Talano
United States
Belgium
Novartis Investigative Site
Recruiting
Gent, 9000
-
Belgium
Canada
Novartis Investigative Site
Recruiting
Calgary, T3B 6A8
Alberta
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
Hamburg, 20246
-
Germany
Novartis Investigative Site
Recruiting
Muenchen, 81377
-
Germany
Italy
Novartis Investigative Site
Recruiting
Monza, 20900
MB
Italy
Novartis Investigative Site
Recruiting
Roma, 00165
RM
Italy
Netherlands
Prinses Maxima Centrum voor Kinderoncologie
Recruiting
Utrecht, 3584 - CS
Contact: R. Pieters
Netherlands
Norway
Novartis Investigative Site
Recruiting
Oslo, 0424
-
Norway
Spain
Novartis Investigative Site
Recruiting
Esplugues de Llobregat, 08950
Barcelona
Spain
Sweden
Novartis Investigative Site
Recruiting
Goteborg, SE 416 85
-
Sweden
Novartis Investigative Site
Recruiting
Stockholm, 141 86
-
Sweden
United Kingdom
Novartis Investigative Site
Recruiting
London, WC1E 6HX
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United Kingdom
Novartis Investigative Site
Recruiting
London, WC1N 3JH
-
United Kingdom

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Phone: 
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