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

• ClinicalTrials.gov Identifier: NCT03568461
• Recruitment Status: Active, not recruiting
• First Posted: June 26, 2018
• Last Update Posted: May 6, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: May 24, 2018
• First Posted Date: June 26, 2018
• Last Update Posted Date: May 6, 2022
• Actual Study Start Date: November 12, 2018
• Actual Primary Completion Date: November 24, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 13, 2018)

Complete response rate (CRR) [ Time Frame: 2 years ]

CRR based on Lugano classification response criteria

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 13, 2018)

• Overall response rate (ORR) [ Time Frame: 2 years ]
  ORR, including complete response (CR) and partial response (PR)
• Duration of response (DOR) [ Time Frame: 2 years ]
  Time from achievement of CR or PR to relapse or death due to follicular lymphoma
• Progression free survival (PFS) [ Time Frame: 2 years ]
  Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause
• Overall survival (OS) [ Time Frame: 2 years ]
  Time from tisagenlecleucel infusion to death due to any cause
• tisagenlecleucel transgene concentration [ Time Frame: 2 years ]
  Transgene concentration as detected by qPCR in target tissue
• Cmax; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
  The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/ µg)
• Tmax; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
  The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)
• AUC0-28; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
  The AUC from time zero to day 28, in peripheral blood (%*days or days*copies/ µg)
• AUC0-84d; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
  The AUC from time zero to day 84, in peripheral blood (%*days or days*copies/ µg)
• T1/2; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
  The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood
• Tlast; cellular kinetic parameter of tisagenlecleucel [ Time Frame: 2 years ]
  The last observed measureable timepoint after dose administration
• Summary of exposure of CD3+ tisagenlecleucel cells in peripheral blood [ Time Frame: 2 years ]
  In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry
• humoral immunogenicity [ Time Frame: 2 years ]
  Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
• cellular immunogenicity [ Time Frame: 2 years ]
  Presence of T lymphocytes activated by the tisagenlecleucel protein
• Summary scores of PRO measured by SF-36v2 quality of life questionnaire [ Time Frame: 2 years ]
  Effect of tisagenlecleucel therapy on Patient reported outcomes
• Summary scores of PRO measured by EQ-5D-3L quality of life questionnaire [ Time Frame: 2 years ]
  Effect of tisagenlecleucel therapy on Patient reported outcomes
• Summary scores of PRO measured by FACT-Lym quality of life questionnaire [ Time Frame: 2 years ]
  Effect of tisagenlecleucel therapy on Patient reported outcomes

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma
• Official Title: 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
• Brief Summary: This is a multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory FL.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Follicular Lymphoma

Intervention

Biological: tisagenlecleucel

single infusion

Study Arms

Experimental: CTL019

tisagenlecleucel infusion

Intervention: Biological: tisagenlecleucel

• Publications *: 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, Pérez-Simón 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 1, 2021): 97
• Original Estimated Enrollment (submitted: June 13, 2018): 113
• Estimated Study Completion Date: May 22, 2025
• Actual Primary Completion Date: November 24, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, France, Germany, Italy, Japan, Netherlands, Norway, Spain, United Kingdom, United States
• Removed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT03568461
• Other Study ID Numbers: CCTL019E2202; 2017-004385-94 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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.

• URL: https://www.clinicalstudydatarequest.com

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: April 2022