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Non-Hodgkin LymphomaPhase 3BELINDANCT03570892

Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma

A Phase 3 study testing Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy and Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT) in people with Non-Hodgkin Lymphoma, run by Novartis Pharmaceuticals at 67 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Non-Hodgkin Lymphoma
What is being tested?
Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy and Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
330 participants
Where
67 sitesin 18 countries
Study dates
9 May 2019to 3 Feb 2026
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
Show all 36Show fewer
  • 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
  • Relapse or progression within 365 days from last dose of anti CD20 antibody and anthracycline containing first line immunochemotherapy or refractory (have not achieved a CR).
  • Patient is considered eligible for autologous HSCT as per local investigator assessment. Note: Intention to transplant and type of high dose chemotherapy (HDCT) regimen will be documented at the time of study entry
  • Disease that is both active on PET scan (defined as 5-Deauville scorepoint-scale of 4 or 5) and measurable on CT scan, defined as::
  • Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or
  • Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate organ function:
  • Renal function defined as:
  • Serum creatinine of ≤1.5 x upper limit of normal (ULN), OR estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2
  • Hepatic function defined as:
  • Alanine Transaminase (ALT) and Aspartate Transiminase (AST) ≤ 5 × ULN
  • Total bilirubin ≤ 1.5 x ULN with the exception of patients with Gilbert syndrome who may be included if their total bilirubin is ≤3.0 × ULN and direct bilirubin ≤1.5 × ULN
  • Hematologic Function (regardless of transfusions) defined as:
  • Absolute neutrophil count (ANC) >1000/mm3
  • Absolute lymphocyte count (ALC) >300/mm3 OR Absolute number of CD3+ T cells >150/mm3 (only for patients with non-historical apheresis)
  • Platelets ≥50000/mm3
  • Hemoglobin >8.0 g/dl
  • Adequate pulmonary function defined as:
  • No or mild dyspnea (≤ Grade 1)
  • Oxygen saturation measured by pulse oximetry > 90% on room air
  • Forced expiratory volume in 1 s (FEV1) ≥ 50% and/or carbon monoxide diffusion test (DLCO) ≥50% of predicted level - Must have a leukapheresis material of non-mobilized cells available for manufacturing.

Who cannot join

  • 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:
Show all 15Show fewer
  • 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))

Trial locations and contacts

67 sites in 18 countries.

67 sites in 18 countries

United States22 sites

  • Emory University

    Atlanta, Georgia, 30329

  • St Davids South Austin Medical Ctr

    Austin, Texas, 78704

  • MUSC Hollings Cancer Center

    Charleston, South Carolina, 29425

  • Tennessee Oncology PLLC

    Chattanooga, Tennessee, 37404

  • Uni of Chi Medi Ctr Hema and Onco

    Chicago, Illinois, 60637

  • Jewish Hospital

    Cincinnati, Ohio, 45236

  • The Ohio State University

    Columbus, Ohio, 43210

  • Texas Oncology-Baylor Scott and White

    Dallas, Texas, 75231

  • Sarah Cannon Research Institute

    Denver, Colorado, 80218

  • Wayne State University-Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Hackensack Uni Medical Center

    Hackensack, New Jersey, 07601

  • Uni of Texas MD Anderson Ca Center

    Houston, Texas, 77030

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66205

  • Moores UC San Diego Cancer Center

    La Jolla, California, 92093

  • University of California Los Angeles

    Los Angeles, California, 90095

  • Uni of Wisconsin Carbone Cancer Ctr

    Madison, Wisconsin, 53792-6164

  • Uni of Nebraska Med Ctr

    Omaha, Nebraska, 68198

  • Uni Pennsylvania Abramson Cncr Ctr

    Philadelphia, Pennsylvania, 19104

  • Oregon Health Sciences Univ

    Portland, Oregon, 97239

  • Methodist Hospital

    San Antonio, Texas, 78229

  • UCSF Medical Center

    San Francisco, California, 94143

Other trials in United States

Germany7 sites

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Cologne, North Rhine-Westphalia, 50937

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Leipzig, Saxony, 04103

  • Novartis Investigative Site

    Munich, Bavaria, 81377

  • Novartis Investigative Site

    Regensburg, Bavaria, 93053

  • Novartis Investigative Site

    Ulm, 89081

Other trials in Germany

France6 sites

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Montpellier, 34295

  • Novartis Investigative Site

    Nantes, 44093

  • Novartis Investigative Site

    Paris, 75475

  • Novartis Investigative Site

    Pierre-Bénite, 69495

  • Novartis Investigative Site

    Toulouse, 31059

Other trials in France

Spain5 sites

  • Novartis Investigative Site

    Barcelona, 08035

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Novartis Investigative Site

    Madrid, 28009

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Salamanca, 37007

Other trials in Spain

Australia3 sites

  • Novartis Investigative Site

    Darlinghurst, New South Wales, 2010

  • Novartis Investigative Site

    Melbourne, Victoria, 3000

  • Novartis Investigative Site

    Murdoch, Western Australia, 6150

Other trials in Australia

China3 sites

  • Novartis Investigative Site

    Beijing, 100036

  • Novartis Investigative Site

    Beijing, 100191

  • Novartis Investigative Site

    Shanghai, 200065

Other trials in China

Italy3 sites

  • Novartis Investigative Site

    Milan, MI, 20133

  • Novartis Investigative Site

    Roma, RM, 00168

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Japan3 sites

  • Novartis Investigative Site

    Fukuoka, 8128582

  • Novartis Investigative Site

    Sapporo, Hokkaido, 060-8648

  • Novartis Investigative Site

    Sendai, Miyagi, 9808574

Other trials in Japan

Austria2 sites

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Brazil2 sites

  • Novartis Investigative Site

    Salvador, Estado de Bahia, 41253-190

  • Novartis Investigative Site

    São Paulo, 05651-901

Other trials in Brazil

Netherlands2 sites

  • Novartis Investigative Site

    Amsterdam, North Holland, 1081 HV

  • Novartis Investigative Site

    Utrecht, 3584 CX

Other trials in Netherlands

Singapore2 sites

  • Novartis Investigative Site

    Singapore, 119074

  • Novartis Investigative Site

    Singapore, 169608

Other trials in Singapore

United Kingdom2 sites

  • Novartis Investigative Site

    Birmingham, West Midlands, B15 2TH

  • Novartis Investigative Site

    London, NW1 2BU

Other trials in United Kingdom

Belgium1 site

  • Novartis Investigative Site

    Leuven, 3000

Other trials in Belgium

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong, 999077

Other trials in Hong Kong

Norway1 site

  • Novartis Investigative Site

    Oslo, 0310

Other trials in Norway

Switzerland1 site

  • Novartis Investigative Site

    Zurich, 8091

Other trials in Switzerland

Taiwan1 site

  • Novartis Investigative Site

    Taipei, 10002

Other trials in Taiwan

About this study

Official title: 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)

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.

Read the detailed description

Approximately 318 subjects were planned to be randomized; 322 subjects were analyzed (Full analysis set): 162 subjects in the tisagenlecleucel arm and 160 subjects in the SOC arm.

The target population consisted of adult participants with aggressive B-cell non-Hodgkin lymphoma (NHL) who were relapsed/refractory within 365 days of their last dose of first line immunochemotherapy and eligible for autologous hematopoietic stem cell transplantation (HSCT).

The duration of treatment in the tisagenlecleucel treatment strategy is from the start of bridging chemotherapy (if applicable) until the infusion of tisagenlecleucel (expected on average at approximately 6 weeks from randomization). The duration of the treatment in the SOC treatment strategy is from the start of salvage chemotherapy until autologous HSCT. In either treatment arm, if infusion of tisagenlecleucel or autologous HSCT is not possible, the duration of treatment is until the last dose of study treatment prior to discontinuation of the treatment strategy.

Being tested
Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy, Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)
Keywords
Non-Hodgkin's Lympoma, B-Cell Lymphoma, Diffuse Large B-cell Lymphoma, High Grade B-cell Lymphoma, Follicular Lymphoma grade 3B, CAR-T, Tisagenlecleucel, Kymriah, Immunotherapy, Cellular therapy, CTL019
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tisagenlecleucel after optional bridging and lymphodepleting chemotherapyDrug

    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)

  • Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)Drug

    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

Study groups in NCT03570892
Study groupRoleWhat they receive
Tisagenlecleucel treatment strategyExperimentalPatients received investigator's choice of optional platinum-based immunochemotherapy followed by lymphodepleting chemotherapy and a single dose of tisagenlecleucel
Receives: Drug: Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy
Standard of care treatment strategyActive comparatorPatients received investigator's choice of platinum-based immunochemotherapy followed in responding patients by high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)
Receives: Drug: Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: appro. 24 months

Secondary outcomes (11)

  1. Event Free Survival (EFS) as Assessed by Local Investigator

    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.

    Measured: 5 years

  2. Overall Survival (OS)

    Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause

    Measured: 5 years

  3. Overall Response Rate (ORR)

    Overall Response Rate (ORR) as per the Lugano criteria as per BIRC review and local investigator assessment

    Measured: 5 years

  4. Duration of Response (DOR)

    Duration of response: time from the date of first documented response of CR or PR to the date of first documented progression (SD or PD at or after the week 12 assessment will be considered progression) or death due to aggressive B-cell NHL. DOR will be summarized by BIRC and local response

    Measured: 5 years

  5. Time to Response (TTR)

    Time from the date of randomization to the date of a patient's first achieved a response of CR or PR on or after the Week 12 assessment

    Measured: 5 years

  6. SF-36v2

    Time to definitive deterioration in SF-36v2

    Measured: 24 Months

  7. FACT-Lym

    Time to definitive deterioration in FACT-Lym

    Measured: 24 Months

  8. EQ-VAS

    Time to definitive deterioration in EQ-VAS

    Measured: 24 Months

  9. Tisagenlecleucel Transgene Concentrations

    qPCR will be used to measure tisagenlecleucel transgene concentrations in peripheral blood and bone marrow

    Measured: 5 years

  10. Tisagenlecleucel Immunogenicity (Humoral and Cellular)

    Pre-existing and treatment related immunogenicity (humoral and cellular) of tisagenlecleucel will be characterized.

    Measured: 5 years

  11. Presence of Replication Competent Lentivirus (RCL)

    The presence of RCL will be assessed by VSV-qPCR in patients receiving tisagenlecleucel

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2018
  2. Study start9 May 2019
  3. Primary completion6 May 2021
  4. Study completion3 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, Open-Label
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
330 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03570892
Sponsor's protocol ID
CCTL019H2301
Other IDs
2016-002966-29, 2023-508343-48-00, 2023, 2016
Acronym
BELINDA
Status last verified
Jun 2026
First submitted
18 Jun 2018
Last updated
12 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 34904798

  • 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.

    PubMed 34515338

  • Thiruvengadam 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.

    PubMed 33288485

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy and Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT) in people with Non-Hodgkin Lymphoma, run by Novartis Pharmaceuticals at 67 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 67 sites in United States, Germany, France, Spain, Australia and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (EFS) Per Blinded Independent Review Committee (BIRC) Assessment (time frame: appro. 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03570892, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.

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