Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients
BIANCA
A Phase II, Single Arm, Multicenter Open Label Trial to Determine the Safety and Efficacy of Tisagenlecleucel in Pediatric Subjects With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma (NHL)
2 other identifiers
interventional
34
13 countries
24
Brief Summary
The purpose of the study was to assess the efficacy and safety of tisagenlecleucel in pediatric, adolescent and young adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) including Burkitt Lymphoma and Burkitt Leukemia. For pediatric patients who have r/r B-NHL including Burkitt Lymphoma and Burkitt Leukemia, survival rates are dismal, only \~20-50% subjects are alive at 2 years with overall response rate (ORR) of 20-30% after conventional salvage chemotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2019
Typical duration for phase_2
24 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
July 13, 2018
CompletedFirst Posted
Study publicly available on registry
August 1, 2018
CompletedStudy Start
First participant enrolled
February 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 27, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
April 26, 2023
CompletedResults Posted
Study results publicly available
March 19, 2024
CompletedJune 20, 2024
June 1, 2024
2.4 years
July 13, 2018
October 25, 2023
June 17, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR) as Determined by Local Investigator
The overall response rate (ORR) is defined as the percentage of subjects with a best overall disease response of complete response (CR) or partial response (PR), where the best overall disease response is defined as the best disease response recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever comes first.
6 months post-tisagenlecleucel infusion
Secondary Outcomes (13)
Duration of Response (DOR)
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Event Free Survival (EFS)
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Relapse Free Survival (RFS)
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Progression Free Survival (PFS)
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
Overall Survival (OS)
Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48
- +8 more secondary outcomes
Study Arms (1)
Tisagenlecleucel
EXPERIMENTALParticipants were infused once with CAR-positive viable T cells
Interventions
Tisagenlecleucel was infused once as an intravenous infustion at a dose of either 0.2 to 5 x 106 CAR-positive viable T cells per kg body weight for subjects ≤ 50 kg or 0.1 to 2.5 x 108 CAR-positive viable T cells for subjects \> 50 kg.
Prior to tisagenlecleucel infusion, each subject underwent lymphodepletion with recommended Fludarabine and cyclophosphamide (unless contra-indicated for subject)
Pre-treatment phase could also include bridging therapy of investigator's choice
Eligibility Criteria
You may qualify if:
- Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL) including the following subtypes; Burkitt lymphoma/ Burkitt leukemia (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), and follicular lymphoma (FL) Note: Patients with B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
- Patients \<25 years of age and weighing at least 6 kg at the time of screening
- Patients who have relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant) or are primary refractory (have not achieved a CR or PR after the first line of therapy)
- Measurable disease by radiological criteria in all patients at the time of screening. Patients with Burkitt leukemia who don't meet radiological criteria must have bone marrow involvement of \>25% by local assessment of bone marrow aspirate and/or biopsy.
- Karnofsky (age ≥16 years) or Lansky (age \<16 years) performance status ≥60.
- Adequate bone marrow reserve without transfusions (transfusion \>2 weeks prior to laboratory assessment is allowed) defined as:
- Absolute neutrophil count (ANC) \>1000/mm3
- Platelets ≥50000//mm3
- Hemoglobin ≥8.0 g/dl
- Adequate organ function defined as:
- a serum creatinine (sCR) based on gender/age as follows: Maximum Serum Creatinine (mg/dL) Age Male Female
- to \<2 years 0.6 0.6 2 to \<6 years 0.8 0.8 6 to \<10 years 1.0 1.0 10 to \<13 years 1.2 1.2 13 to \<16 years 1.5 1.4
- ≥16 years 1.7 1.4
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN) for age
- Total bilirubin \<2 mg/dL (for Gilbert's Syndrome patients total bilirubin \<4 mg/dL)
- +3 more criteria
You may not qualify if:
- Prior gene therapy or engineered T cell therapy.
- Prior treatment with any anti-CD19 therapy.
- Allogeneic hematopoietic stem cell transplant (HSCT) \<3 months prior to screening and ≤4 months prior to infusion.
- Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) in patients who received prior allogeneic HSCT.
- Prior diagnosis of malignancy other than study indication, and not disease free for 5 years.
- Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.)
- Presence of active hepatitis B or C as indicated by serology.
- Human Immunodeficiency Virus (HIV) positive test.
- Active neurological autoimmune or inflammatory disorders not related to B cell NHL (eg: Guillain-Barre syndrome, Amyotrophic Lateral Sclerosis)
- Active central nervous system (CNS) involvement by malignancy.
- Patients with B-cell NHL in the context of post-transplant lymphoproliferative disorders (PTLD) associated lymphomas.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Childrens Hospital Los Angeles
Los Angeles, California, 90027, United States
UCSF Medical Center
San Francisco, California, 94143, United States
Johns Hopkins Oncology Center ORA
Baltimore, Maryland, 21231, United States
Dana Farber Cancer Institute Dept.of DFCI
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center MSKCC (8)
New York, New York, 10065, United States
Cinn Children Hosp Medical Center
Cincinnati, Ohio, 45229-3039, United States
The Childrens Hospital of Philadelphia Drug Shipment
Philadelphia, Pennsylvania, 19104, United States
University of Texas Southwestern Medical Center .
Dallas, Texas, 75235, United States
Novartis Investigative Site
Randwick, New South Wales, 2031, Australia
Novartis Investigative Site
Parkville, Victoria, 3052, Australia
Novartis Investigative Site
Vienna, A 1090, Austria
Novartis Investigative Site
Toronto, Ontario, M5G 1X8, Canada
Novartis Investigative Site
Copenhagen, 2100, Denmark
Novartis Investigative Site
Helsinki, 00029, Finland
Novartis Investigative Site
Paris, 75019, France
Novartis Investigative Site
Villejuif, 94800, France
Novartis Investigative Site
Münster, 48149, Germany
Novartis Investigative Site
Monza, MB, 20900, Italy
Novartis Investigative Site
Roma, RM, 00165, Italy
Kyoto University Hospital
Sakyō-ku, Kyoto, 606 8507, Japan
Novartis Investigative Site
Setagaya-ku, Tokyo, 157-8535, Japan
Prinses Maxima Centrum voor Kinderoncologie
Utrecht, CS, 3584, Netherlands
Novartis Investigative Site
Oslo, 0424, Norway
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Madrid, 28046, Spain
Novartis Investigative Site
London, WC1N 1EH, United Kingdom
Related Publications (1)
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 13, 2018
First Posted
August 1, 2018
Study Start
February 15, 2019
Primary Completion
July 27, 2021
Study Completion
April 26, 2023
Last Updated
June 20, 2024
Results First Posted
March 19, 2024
Record last verified: 2024-06
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.