Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma
BELINDA
Tisagenlecleucel Versus Standard of Care in Adult Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma: A Randomized, Open Label, Phase III Trial (BELINDA)
3 other identifiers
interventional
330
17 countries
70
Brief Summary
This is a randomized, open label, multicenter phase III trial comparing the efficacy, safety, and tolerability of tisagenlecleucel to Standard Of Care in adult patients with aggressive B-cell Non-Hodgkin Lymphoma after failure of rituximab and anthracycline containing frontline immunochemotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2019
Longer than P75 for phase_3
70 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
June 18, 2018
CompletedFirst Posted
Study publicly available on registry
June 27, 2018
CompletedStudy Start
First participant enrolled
May 7, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 6, 2021
CompletedResults Posted
Study results publicly available
July 23, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 3, 2026
CompletedApril 8, 2026
March 1, 2026
2 years
June 18, 2018
May 7, 2024
March 19, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Event-free Survival (EFS) Per Blinded Independent Review Committee (BIRC) Assessment
Event-free survival (EFS) is defined as the time from the date of randomization to the date of the first documented disease progression or stable disease at or after the week 12 (+/- 1 week) assessment, as assessed by Blinded Independent Review Committee (BIRC) per Lugano criteria, or death due to any cause, at any time.
appro. 24 months
Secondary Outcomes (11)
Event Free Survival (EFS) as Assessed by Local Investigator
5 years
Overall Survival (OS)
5 years
Overall Response Rate (ORR)
5 years
Duration of Response (DOR)
5 years
Time to Response (TTR)
5 years
- +6 more secondary outcomes
Study Arms (2)
Tisagenlecleucel treatment strategy
EXPERIMENTALPatients received investigator's choice of optional platinum-based immunochemotherapy followed by lymphodepleting chemotherapy and a single dose of tisagenlecleucel
Standard of care treatment strategy
ACTIVE COMPARATORPatients received investigator's choice of platinum-based immunochemotherapy followed in responding patients by high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)
Interventions
Investigator's choice of optional platinum-based immunochemotherapy (ie. R-ICE, R-GemOx, R-GDP, R-DHAP) + Lymphodepleting chemotherapy (fludarabine with cyclophosphamide or bendamustine) + Tisagenlecleucel (a second generation CAR-T composed of a CD19 antigen-binding domain, a 4-1BB costimulatory domain and a CD3-ζ signaling domain)
Investigator's choice of platinum-based immunochemotherapy (ie. R-ICE, R-GemOx, R-GDP, R-DHAP)+ High dose chemotherapy (ie. BEAM) + autologous HSCT. \*Ibrutinib or lenalidomide may be used in patients who are no longer eligible for autologous HSCT after 2 cycles of immunochemotherapy
Eligibility Criteria
You may qualify if:
- Histologically confirmed, aggressive B-cell NHL at relapse/progression or PR after front line therapy. Aggressive B-cell NHL is heretofore defined by the following list of subtypes (Swerdlow et al 2016):
- DLBCL, NOS,
- FL grade 3B,
- Primary mediastinal large B cell lymphoma (PMBCL),
- T cell rich/histiocyte rich large B cell lymphoma (T/HRBCL),
- DLBCL associated with chronic inflammation,
- Intravascular large B-cell lymphoma,
- ALK+ large B-cell lymphoma,
- B-cell lymphoma, unclassifiable, (with features intermediate between DLBCL and classical Hodgkin's Lymphoma (HL)),
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,
- High-grade B-cell lymphoma, NOS
- HHV8+ DLBCL, NOS
- DLBCL transforming from follicular lymphoma
- DLBCL transforming from marginal zone lymphoma
- DLBCL, leg type
- +21 more criteria
You may not qualify if:
- Prior treatment with anti-CD19 therapy, T cell therapy, or any prior gene therapy product
- Treatment with any systemic lymphoma-directed second line anticancer therapy prior to randomization. Only steroids and local irradiation are permitted for disease control
- Patients with active central nervous system (CNS) involvement by disease under study are excluded, except if the CNS involvement has been effectively treated and local treatment was \>4 weeks before randomization
- Prior allogeneic HSCT
- Clinically significant active infection
- Any of the following cardiovascular conditions:
- Unstable angina, myocardial infarction, coronary artery bypass graft (CABG), or stroke within 6 months prior to screening,
- Left ventricle ejection fraction (LVEF) \<45% as determined by echocardiogram (ECHO) or magnetic resonance angiography (MRA) or multigated acquisition (MUGA) at the screening assessment.
- New York Heart Association (NYHA) functional class III or IV (Chavey et al 2001), within the past 12 months.
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II) and third degree AV block unless adequately controlled by pacemaker implantation.
- Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening or inability to determine the QTcF interval
- Risk factors for Torsades de Pointes (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia, or any of the following:
- Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
- Concomitant medication(s) with a "Known Risk of Torsades de Pointes" per crediblemeds.org that cannot be discontinued or replaced by safe alternative medication.
- Patients with active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré Syndrome (GBS), Amyotrophic Lateral Sclerosis (ALS)) and clinically significant active cerebrovascular disorders (e.g. cerebral edema, posterior reversible encephalopathy syndrome (PRES))
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (72)
Moores UC San Diego Cancer Center
La Jolla, California, 92093, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
UCSF Medical Center
San Francisco, California, 94143, United States
Sarah Cannon Research Institute
Denver, Colorado, 80218, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Emory University
Atlanta, Georgia, 30329, United States
Uni of Chi Medi Ctr Hema and Onco
Chicago, Illinois, 60637, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66205, United States
Wayne State University-Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Uni of Nebraska Med Ctr
Omaha, Nebraska, 68198, United States
Hackensack Uni Medical Center
Hackensack, New Jersey, 07601, United States
Jewish Hospital
Cincinnati, Ohio, 45236, United States
The Ohio State University
Columbus, Ohio, 43210, United States
Oregon Health Sciences Univ
Portland, Oregon, 97239, United States
Uni Pennsylvania Abramson Cncr Ctr
Philadelphia, Pennsylvania, 19104, United States
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425, United States
Tennessee Oncology PLLC
Chattanooga, Tennessee, 37404, United States
St Davids South Austin Medical Ctr
Austin, Texas, 78704, United States
Texas Oncology-Baylor Scott and White
Dallas, Texas, 75231, United States
Uni of Texas MD Anderson Ca Center
Houston, Texas, 77030, United States
Methodist Hospital
San Antonio, Texas, 78229, United States
Uni of Wisconsin Carbone Cancer Ctr
Madison, Wisconsin, 53792-6164, United States
Novartis Investigative Site
Darlinghurst, New South Wales, 2010, Australia
Novartis Investigative Site
Melbourne, Victoria, 3000, Australia
Novartis Investigative Site
Murdoch, Western Australia, 6150, Australia
Novartis Investigative Site
Salzburg, 5020, Austria
Novartis Investigative Site
Vienna, 1090, Austria
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Salvador, Estado de Bahia, 41253-190, Brazil
Novartis Investigative Site
São Paulo, 05651-901, Brazil
Novartis Investigative Site
Beijing, 100036, China
Novartis Investigative Site
Beijing, 100191, China
Novartis Investigative Site
Shanghai, 200065, China
Novartis Investigative Site
Lille, 59037, France
Novartis Investigative Site
Montpellier, 34295, France
Novartis Investigative Site
Nantes, 44093, France
Novartis Investigative Site
Paris, 75475, France
Novartis Investigative Site
Pierre-Bénite, 69495, France
Novartis Investigative Site
Toulouse, 31059, France
Novartis Investigative Site
Munich, Bavaria, 81377, Germany
Novartis Investigative Site
Regensburg, Bavaria, 93053, Germany
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937, Germany
Novartis Investigative Site
Leipzig, Saxony, 04103, Germany
Novartis Investigative Site
Berlin, 13353, Germany
Novartis Investigative Site
Hamburg, 20246, Germany
Novartis Investigative Site
Ulm, 89081, Germany
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Rozzano, MI, 20089, Italy
Novartis Investigative Site
Roma, RM, 00168, Italy
Kyushu University Hospital
Fukuoka, Fukuoka, 812-8582, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, 060 8648, Japan
Novartis Investigative Site
Sapporo, Hokkaido, 0608648, Japan
Tohoku University Hospital
Sendai, Miyagi, 980 8574, Japan
Novartis Investigative Site
Sendai, Miyagi, 9808574, Japan
Novartis Investigative Site
Fukuoka, 8128582, Japan
Novartis Investigative Site
Amsterdam, North Holland, 1081 HV, Netherlands
Amsterdam UMC, locatie AMC
Amsterdam, 1105 AZ, Netherlands
Novartis Investigative Site
Utrecht, 3584 CX, Netherlands
UMC Utrecht Cancer Center
Utrecht, 3584CX, Netherlands
Novartis Investigative Site
Oslo, 0310, Norway
Novartis Investigative Site
Singapore, 119074, Singapore
Novartis Investigative Site
Singapore, 169608, Singapore
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Novartis Investigative Site
Barcelona, 08035, Spain
Novartis Investigative Site
Madrid, 28009, Spain
Novartis Investigative Site
Madrid, 28041, Spain
Novartis Investigative Site
Salamanca, 37007, Spain
Novartis Investigative Site
Zurich, 8091, Switzerland
Novartis Investigative Site
Taipei, 10002, Taiwan
Novartis Investigative Site
Birmingham, West Midlands, B15 2TH, United Kingdom
Novartis Investigative Site
London, NW1 2BU, United Kingdom
Related Publications (3)
Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, Kato K, Sureda A, Greil R, Thieblemont C, Morschhauser F, Janz M, Flinn I, Rabitsch W, Kwong YL, Kersten MJ, Minnema MC, Holte H, Chan EHL, Martinez-Lopez J, Muller AMS, Maziarz RT, McGuirk JP, Bachy E, Le Gouill S, Dreyling M, Harigae H, Bond D, Andreadis C, McSweeney P, Kharfan-Dabaja M, Newsome S, Degtyarev E, Awasthi R, Del Corral C, Andreola G, Masood A, Schuster SJ, Jager U, Borchmann P, Westin JR. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):629-639. doi: 10.1056/NEJMoa2116596. Epub 2021 Dec 14.
PMID: 34904798DERIVEDErnst 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: 34515338DERIVEDThiruvengadam SK, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11.
PMID: 33288485DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention 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 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 18, 2018
First Posted
June 27, 2018
Study Start
May 7, 2019
Primary Completion
May 6, 2021
Study Completion
February 3, 2026
Last Updated
April 8, 2026
Results First Posted
July 23, 2024
Record last verified: 2026-03
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.