Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients
CASSIOPEIA
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
2 other identifiers
interventional
121
11 countries
45
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2019
Longer than P75 for phase_2
45 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 12, 2018
CompletedFirst Posted
Study publicly available on registry
March 15, 2019
CompletedStudy Start
First participant enrolled
June 24, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 20, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
October 19, 2027
ExpectedApril 17, 2026
April 1, 2026
6.2 years
November 12, 2018
April 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Disease Free Survival (DFS) rate without censoring for new anticancer therapy, including Stem Cell Transplantation (SCT) while in remission
DFS is defined as the time from the date of tisagenlecleucel infusion to the date of the first documented morphological relapse, occurrence of secondary malignancy or death due to any cause.
5 years after tisagenlecleucel infusion
Overall Survival (OS) rate
OS is defined as the time from date of first tisagenlecleucel infusion to the date of death due to any reason.
4 years after tisagenlecleucel
Secondary Outcomes (28)
Percentage of participants who are disease free without allogeneic stem cell transplant (SCT)
12 months after last infusion
DFS rate with censoring for new anticancer therapy, including SCT, while in remission
5 years
Percentage of participants achieving MRD negative CR or CRi at Month 3
3 months after the tisagenlecleucel infusion.
Pediatric Quality of Life (PedsQL)
5 years
European Quality of Life 5 dimensions (EQ-5D-3L & EQ-5D-Y))
5 years
- +23 more secondary outcomes
Study Arms (1)
Single dose of CTL019
EXPERIMENTALBased 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
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
You may qualify if:
- 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-MĂ¼nster (BFM) consolidation or Phase 1b, and interim maintenance with high-dose methotrexate.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novartis Pharmaceuticalslead
- Children's Oncology Groupcollaborator
Study Sites (45)
Children s Hospital of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
City of Hope National Medical
Duarte, California, 91010, United States
Childrens Hospital Los Angeles
Los Angeles, California, 90027, United States
Mattel Childrens Hospital UCLA
Los Angeles, California, 90095, United States
Childrens Hospital of Orange County
Orange, California, 92868-3874, United States
Rady Children s Hospital
San Diego, California, 92123, United States
UCSF Medical Center
San Francisco, California, 94143, United States
Stanford University Medical Center
Stanford, California, 94304, United States
Childrens Hospital Colorado
Aurora, Colorado, 80045, United States
Childrens National Hospital
Washington D.C., District of Columbia, 20010, United States
Johns Hopkins All Childrens
St. Petersburg, Florida, 33701, United States
Childrens Healthcare of Atlanta
Atlanta, Georgia, 30342, United States
James Whitcomb Riley Hospital For Children
Indianapolis, Indiana, 46202, United States
Johns Hopkins Oncology Center
Baltimore, Maryland, 21231, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Children s Mercy Hospital
Kansas City, Missouri, 64108, United States
Hackensack Uni Medical Center
Hackensack, New Jersey, 07601, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Memorial Sloan Kettering Cancer Ctr
New York, New York, 10065, United States
Columbia University Medical Center
New York, New York, 110032, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cinn Children Hosp Medical Center
Cincinnati, Ohio, 45229-3039, United States
Oregon Health and Science University
Portland, Oregon, 97239-3098, United States
The Childrens Hosp of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Univ of Texas Southwest Med Center
Dallas, Texas, 75390-9034, United States
Texas Childrens Cancer and Hematology Center
Houston, Texas, 77030, United States
Methodist Childrens Hospital
San Antonio, Texas, 78229, United States
University of Utah Clinical Trials Office
Salt Lake City, Utah, 84108, United States
University of Wisconsin Hospital and Clinics Pharmacy/Drug Shipping Address
Madison, Wisconsin, 53792, United States
Childrens Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Novartis Investigative Site
Ghent, 9000, Belgium
Novartis Investigative Site
Calgary, Alberta, T3B 6A8, Canada
Novartis Investigative Site
Toronto, Ontario, M5G 1X8, Canada
Novartis Investigative Site
Montreal, Quebec, H3T 1C5, Canada
Novartis Investigative Site
Copenhagen, DK-2100, Denmark
Novartis Investigative Site
Paris, 75019, France
Novartis Investigative Site
Roma, 165, Italy
Prinses Maxima Centrum voor Kinderoncologie
Utrecht, CS, 3584, Netherlands
Novartis Investigative Site
Utrecht, 3584 CS, Netherlands
Novartis Investigative Site
Oslo, 0424, Norway
Novartis Investigative Site
Esplugues, Barcelona, 08950, Spain
Novartis Investigative Site
Gothenburg, SE 416 85, Sweden
Novartis Investigative Site
London, NW1 2BU, United Kingdom
Novartis Investigative Site
London, WC1N 3JH, United Kingdom
Related Publications (1)
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.
PMID: 32589970DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
November 12, 2018
First Posted
March 15, 2019
Study Start
June 24, 2019
Primary Completion
August 20, 2025
Study Completion (Estimated)
October 19, 2027
Last Updated
April 17, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.