A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma (LEDA)

April 17, 2024 updated by: Novartis Pharmaceuticals

A Randomized, Open-label, Multi-center Phase III Trial Comparing Tisagenlecleucel to Standard of Care in Adult Participants With Relapsed or Refractory Follicular Lymphoma (FL)

This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this phase III study is to verify the clinical benefit of tisagenlecleucel for the treatment of r/r FL by comparing the tisagenlecleucel treatment strategy to standard of care therapy in patients with r/r FL after two or more lines of systemic therapy, with progression-free survival (PFS) as the primary endpoint.

The primary objective is to demonstrate superiority of the tisagenlecleucel treatment strategy over standard of care (SOC) therapy with respect to progression-free survival (PFS) determined by blinded independent review committee (BIRC) based on the Lugano response criteria.

Participants randomized to Arm A (tisagenlecleucel treatment) will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells.

Participants randomized to Arm B (Standard of Care) will receive R2 or R-CHOP based on investigator choice and this has to be determined prior to randomization.

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Australia
      • Camperdown, Australia, NSW
        • Recruiting
        • Novartis Investigative Site
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Novartis Investigative Site
      • Melbourne, Victoria, Australia, 3004
        • Recruiting
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1097
        • Recruiting
        • Novartis Investigative Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 06591
        • Recruiting
        • Novartis Investigative Site
  • Poland
      • Gdansk, Poland, 80-952
        • Recruiting
        • Novartis Investigative Site
      • Lodz, Poland, 93 513
        • Recruiting
        • Novartis Investigative Site
    • Slaskie
      • Gliwice, Slaskie, Poland, 44-101
        • Recruiting
        • Novartis Investigative Site
  • Romania
      • Bucharest, Romania, 022328
        • Recruiting
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 119228
        • Recruiting
        • Novartis Investigative Site
  • Slovakia
    • Slovak Republic
      • Bratislava, Slovak Republic, Slovakia, 833 10
        • Recruiting
        • Novartis Investigative Site
  • Spain
      • Barcelona, Spain, 08041
        • Recruiting
        • Novartis Investigative Site
      • Madrid, Spain, 28034
        • Recruiting
        • Novartis Investigative Site
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Recruiting
        • Novartis Investigative Site
    • Castilla Y Leon
      • Salamanca, Castilla Y Leon, Spain, 37007
        • Recruiting
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Recruiting
        • Novartis Investigative Site
      • Hospitalet de LLobregat, Catalunya, Spain, 08907
        • Recruiting
        • Novartis Investigative Site
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Recruiting
        • Novartis Investigative Site
  • Taiwan
      • Taichung, Taiwan, 40705
        • Recruiting
        • Novartis Investigative Site
      • Taipei, Taiwan, 10002
        • Recruiting
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years at the date of signing the informed consent form.
  2. Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).
  3. Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.
  4. Disease that is both active on Positron emission tomography (PET) scan (defined as a score of 4 or 5 on the Deauville 5-point scale) and measurable on Computed tomography (CT) scan.
  5. ECOG performance status of 0, 1 or 2 at screening.
  6. Adequate hematologic, renal, hepatic and pulmonary organ function at screening.
  7. Must meet the institutional criteria to undergo leukapheresis (unless historical leukapheresis is available).
  8. Must be eligible for treatment with the selected standard of care regimen.

Exclusion Criteria:

  1. Follicular lymphoma grade 3B or evidence of histologic transformation.
  2. Prior treatment with anti-CD19 therapy, gene therapy, or adoptive T-cell therapy.
  3. Active CNS involvement by malignancy.
  4. Clinically significant active infection, presence of Human immunodeficiency virus (HIV) antibody or active hepatitis B or C.
  5. Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome).
  6. Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to randomization.
  7. Clinically significant cardiovascular conditions such as acute coronary syndrome, significant cardiac arrhythmias, heart failure or decreased LVEF.

Other protocol defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tisagenlecleucel
Participants randomized to the tisagenlecleucel treatment strategy will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells
Biological: Tisagenlecleucel
Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells taken intravenously (i.v.).
Other Names:
  • CTL019
Drug: Lymphodepleting chemotherapy

Fludarabine (25 mg/m^2 intravenously [i.v.] daily for 3 doses) OR Cyclophosphamide (250 mg/m^2 i.v. daily for 3 doses starting with the first dose of fludarabine).

OR Bendamustine 90 mg/m^2 i.v. daily for 2 days (If there was previous grade IV hemorrhagic cystitis with cyclophosphamide, or the participant demonstrated resistance to a previous cyclophosphamide-containing regimen)

Other: Corticosteroids and/or Radiation (Bridging therapy)
Corticosteroids and/or Radiation
Active Comparator: R2 or R-CHOP
Participants randomized to Standard of Care treatment will receive either R2 or R-CHOP based on investigator choice of therapies, and this has to be determined prior to randomization.
Drug: Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.
Lenalidomide 20 mg daily on days 1-21 for up to 12 cycles Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-5
Other Names:
  • R2
Drug: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles
Rituximab 375 mg/m2 i.v. on day 1 Cyclophosphamide 750 mg/m2 i.v. day 1 Doxorubicin 50 mg/m2 i.v. day 1 Vincristine 1.4 mg/2 (capped at 2 mg) i.v. day 1 Prednisone or prednisolone 40 mg/m2 PO days 1-5
Other Names:
  • R-CHOP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
Time Frame: 5 years

Progression free survival (PFS) based on Lugano response criteria, defined as time from randomization to the first of the following events to occur:

  • progressive disease (by BIRC)
  • death from any cause
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rate (CRR) as assessed by BIRC (Key Secondary)
Time Frame: 5 years
CRR: The proportion of participants with BOR of complete response (CR)
5 years
Overall response rate (ORR) by BIRC
Time Frame: 5 years
ORR: The proportion of participants with BOR of either CR or partial response (PR)
5 years
Overall survival (OS)
Time Frame: 5 years
OS: Time from randomization to date of death due to any cause
5 years
Time to next anti-lymphoma treatment (TTNT)
Time Frame: 5 years
TTNT: Time from randomization until start of new anticancer therapy or death due to any cause.
5 years
Duration of Response (DOR)
Time Frame: 5 years
Time from the date of first documented BIRC response of CR or PR to the date of first documented progression by BIRC or any cause of death
5 years
Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)
Time Frame: 5 years
Summarize percentage of patients with pre-existing and treatment-induced anti-mCAR antibodies, and relate the antibody responses with CAR expansion, efficacy, and safety endpoints.
5 years
Anti-mCAR, T cell response, as measured by IFNγ expression (cellular immunogenicity)
Time Frame: 5 years
Summarize cellular immunogenicity by pre-infusion and post-infusion timepoints, and correlate cellular immunogenicity signals with CAR expansion, efficacy, and safety endpoints.
5 years
CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)
Time Frame: 5 years
Summary of transgene levels by timepoints and by clinical responses, cellular kinetic parameters will be derived using non-compartmental analysis from time course of transgene levels and will be summarized by clinical responses.
5 years
Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel
Time Frame: 5 years
This is to assess presence of (Replication competent lentivirus) RCL in participants receiving tisagenlecleucel by VSV-g qPCR
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 2, 2023

Primary Completion (Estimated)

July 24, 2028

Study Completion (Estimated)

February 7, 2029

Study Registration Dates

First Submitted

May 1, 2023

First Submitted That Met QC Criteria

May 24, 2023

First Posted (Actual)

June 5, 2023

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 17, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCTL019E2301
  • 2023-503452-27-00 (Registry Identifier: EU CT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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