Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma (ELARA)

A Phase II, Single Arm, Multicenter Open Label Trial to Determine the Efficacy and Safety of Tisagenlecleucel (CTL019) in Adult Patients With Refractory or Relapsed Follicular Lymphoma

This is a multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory FL.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Biological: tisagenlecleucel

Detailed Description

This single-arm, open label study had the following sequential phases: Screening, Pretreatment, Treatment and Follow-up. In the Pre-treatment phase, the patient could undergo bridging therapy (optional) and lymphodepleting (LD) chemotherapy. Treatment and Follow-up Phase included tisagenlecleucel infusion, and safety and efficacy follow-up for at least 24 months. For all the patients who received tisagenlecleucel infusion, additional survival follow-up was to be performed to determine survival status every 3 months.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, QLD 4006
    • Novartis Investigative Site
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novartis Investigative Site
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
• Austria
  • Linz, Austria, 4020
    • Novartis Investigative Site
• Belgium
  • Ghent, Belgium, 9000
    • Novartis Investigative Site
• France
  • Paris, France, 75475
    • Novartis Investigative Site
  • Pierre-Bénite, France, 69495
    • Novartis Investigative Site
• Germany
  • Cologne, Germany, 50937
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Bavaria
    • Munich, Bavaria, Germany, 81377
      • Novartis Investigative Site
• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • MI
    • Milan, MI, Italy, 20132
      • Novartis Investigative Site
• Japan
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060 8648
      • Novartis Investigative Site
  • Miyagi
    • Sendai, Miyagi, Japan, 980 8574
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC, locatie AMC
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Novartis Investigative Site
• Norway
  • Oslo, Norway, 0310
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
• United States
  • California
    • Duarte, California, United States, 91010 3000
      • City of Hope National Medical Center
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Uni of Chi Medi Ctr Hema and Onco
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Univ of Kansas Hosp and Med Ctr
  • Michigan
    • Ann Arbor, Michigan, United States, 48109 5271
      • Michigan Med University of Michigan
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Clinical
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Refractory or relapsed Follicular Lymphoma (Grade 1, 2, 3A)
• Radiographically measurable disease at screening

Exclusion Criteria:

• Evidence of histologic transformation
• Follicular Lymphoma Grade 3B
• Prior anti-CD19 therapy
• Prior gene therapy
• Prior adoptive T cell therapy
• Prior allogeneic hematopoietic stem cell transplant
• Active CNS involvement by malignancy

Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTL019; All patients who received tisagenlecleucel infusion.	Biological: tisagenlecleucel; Tisagenlecleucel is single infusion.; Other Names: CTL019

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment	Complete response rate was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever came first. CRR was determined by an independent review committee (IRC) and was based on Lugano 2014 classification response criteria. The radiological response is first obtained from CT and PET studies according to the Lugano 2014 criteria. CT response is based on anatomical measurements of index/non-index/new lesions and spleen length. The possible response outcomes are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). PET response based on a 5-point scale (5PS) or Deauville score. The possible outcomes for PET response are complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) Per IRC Assessment	Overall response rate is defined as the percentage of participants with a best overall disease response of complete response (CR) or partial response (PR). Response was evaluated per Lugano 2014 classification response criteria. The radiological response is first obtained from CT and PET studies according to the Lugano 2014 criteria. CT response is based on anatomical measurements of index/non-index/new lesions and spleen length. The possible response outcomes are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). PET response based on a 5-point scale (5PS) or Deauville score. The possible outcomes for PET response are complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD).	1 year
Duration of Response (DOR) Per IRC	Duration of response (DOR) applied only to participants whose best overall disease response was CR or PR. It is defined as the time from the date of first documented disease response (CR or PR) to the date of first documented progression or death due to follicular lymphoma (FL).	1 year
Progression Free Survival (PFS)	Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause	2 years
Overall Survival (OS)	Time from tisagenlecleucel infusion to death due to any cause	2 years
Tisagenlecleucel Transgene Concentration	Transgene concentration as detected by qPCR in target tissue	2 years
Cmax; Cellular Kinetic Parameter of Tisagenlecleucel	The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/ µg)	2 years
Tmax; Cellular Kinetic Parameter of Tisagenlecleucel	The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)	2 years
AUC0-28; Cellular Kinetic Parameter of Tisagenlecleucel	The AUC from time zero to day 28, in peripheral blood (%*days or days*copies/ µg)	2 years
AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel	The AUC from time zero to day 84, in peripheral blood (%*days or days*copies/ µg)	2 years
T1/2; Cellular Kinetic Parameter of Tisagenlecleucel	The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood	2 years
Tlast; Cellular Kinetic Parameter of Tisagenlecleucel	The last observed measureable timepoint after dose administration	2 years
Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood	In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry	2 years
Humoral Immunogenicity	Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.	2 years
Cellular Immunogenicity	Presence of T lymphocytes activated by the tisagenlecleucel protein	2 years
Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire	Effect of tisagenlecleucel therapy on Patient reported outcomes	2 years
Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire	Effect of tisagenlecleucel therapy on Patient reported outcomes	2 years
Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire	Effect of tisagenlecleucel therapy on Patient reported outcomes	2 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Salles G, Schuster SJ, Dreyling M, Fischer L, Kuruvilla J, Patten PEM, von Tresckow B, Smith SM, Jimenez-Ubieto A, Davis KL, Anjos C, Chu J, Zhang J, Lobetti Bodoni C, Thieblemont C, Fowler NH, Dickinson M, Martinez-Lopez J, Wang Y, Link BK. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. 2022 Nov 22;6(22):5835-5843. doi: 10.1182/bloodadvances.2022008150.
• Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, Ghosh M, Popplewell L, Chavez JC, Bachy E, Kato K, Harigae H, Kersten MJ, Andreadis C, Riedell PA, Ho PJ, Perez-Simon JA, Chen AI, Nastoupil LJ, von Tresckow B, Ferreri AJM, Teshima T, Patten PEM, McGuirk JP, Petzer AL, Offner F, Viardot A, Zinzani PL, Malladi R, Zia A, Awasthi R, Masood A, Anak O, Schuster SJ, Thieblemont C. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022 Feb;28(2):325-332. doi: 10.1038/s41591-021-01622-0. Epub 2021 Dec 17.
• Dreyling M, Fowler NH, Dickinson M, Martinez-Lopez J, Kolstad A, Butler J, Ghosh M, Popplewell L, Chavez JC, Bachy E, Kato K, Harigae H, Kersten MJ, Andreadis C, Riedell PA, Ho PJ, Perez-Simon JA, Chen AI, Nastoupil LJ, von Tresckow B, Maria Ferreri AJ, Teshima T, Patten PEM, McGuirk JP, Petzer AL, Offner F, Viardot A, Zinzani PL, Malladi R, Paule I, Zia A, Awasthi R, Han X, Germano D, O'Donovan D, Ramos R, Maier HJ, Masood A, Thieblemont C, Schuster SJ. Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update. Blood. 2024 Apr 25;143(17):1713-1725. doi: 10.1182/blood.2023021567.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2018
• Primary Completion (Actual): November 24, 2020
• Study Completion (Actual): May 28, 2025

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; Relapsed; Refractory; CTL019; Follicular lymphoma; Chimeric antigen receptor; Tisagenlecleucel; Refractory or relapsed Follicular Lymphoma; CAR19
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Follicular; Antineoplastic Agents, Immunological; Antineoplastic Agents; tisagenlecleucel
• Other Study ID Numbers: CCTL019E2202; 2017-004385-94 (EudraCT Number); 2023-508127-13-00 (Registry Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No