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

NCT ID: NCT05888493

Last Updated: 2025-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

108 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-02

Study Completion Date

2031-01-18

Brief Summary

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

Detailed Description

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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.

Conditions

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Follicular Lymphoma (FL)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Tisagenlecleucel

Intervention Type BIOLOGICAL

Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10\^8 CAR-positive viable T-cells taken intravenously (i.v.).

Lymphodepleting chemotherapy

Intervention Type DRUG

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)

Corticosteroids and/or Radiation (Bridging therapy)

Intervention Type OTHER

Corticosteroids and/or Radiation

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.

Group Type ACTIVE_COMPARATOR

Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.

Intervention Type DRUG

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

Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles

Intervention Type DRUG

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

Interventions

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Tisagenlecleucel

Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10\^8 CAR-positive viable T-cells taken intravenously (i.v.).

Intervention Type BIOLOGICAL

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

Intervention Type 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

Intervention Type 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)

Intervention Type DRUG

Corticosteroids and/or Radiation (Bridging therapy)

Corticosteroids and/or Radiation

Intervention Type OTHER

Other Intervention Names

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CTL019 R2 R-CHOP

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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TRIHEALTH Good Samarithan Hospital

Cincinnati, Ohio, United States

Site Status RECRUITING

VA Tennessee Valley Healthcare System

Nashville, Tennessee, United States

Site Status RECRUITING

Novartis Investigative Site

Camperdown, New South Wales, Australia

Site Status RECRUITING

Novartis Investigative Site

Clayton, Victoria, Australia

Site Status RECRUITING

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status RECRUITING

Novartis Investigative Site

Nedlands, Western Australia, Australia

Site Status RECRUITING

Novartis Investigative Site

Linz, , Austria

Site Status RECRUITING

Novartis Investigative Site

Salzburg, , Austria

Site Status RECRUITING

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status RECRUITING

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status RECRUITING

Novartis Investigative Site

Ostrava, Poruba, Czechia

Site Status RECRUITING

Novartis Investigative Site

Budapest, , Hungary

Site Status RECRUITING

Novartis Investigative Site

Poznan, Greater Poland Voivodeship, Poland

Site Status RECRUITING

Novartis Investigative Site

Gliwice, Silesian Voivodeship, Poland

Site Status RECRUITING

Novartis Investigative Site

Gdansk, , Poland

Site Status RECRUITING

Novartis Investigative Site

Lodz, , Poland

Site Status RECRUITING

Novartis Investigative Site

Bucharest, , Romania

Site Status RECRUITING

Novartis Investigative Site

Singapore, , Singapore

Site Status RECRUITING

Novartis Investigative Site

Bratislava, , Slovakia

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status RECRUITING

Novartis Investigative Site

Seoul, , South Korea

Site Status COMPLETED

Novartis Investigative Site

Santiago Compostela, A Coruna, Spain

Site Status RECRUITING

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status RECRUITING

Novartis Investigative Site

Santander, Cantabria, Spain

Site Status RECRUITING

Novartis Investigative Site

Salamanca, Castille and León, Spain

Site Status RECRUITING

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status RECRUITING

Novartis Investigative Site

El Palmar, Murcia, Spain

Site Status RECRUITING

Novartis Investigative Site

Barcelona, , Spain

Site Status RECRUITING

Novartis Investigative Site

Córdoba, , Spain

Site Status RECRUITING

Novartis Investigative Site

Madrid, , Spain

Site Status RECRUITING

Novartis Investigative Site

Kaohsiung City, , Taiwan

Site Status RECRUITING

Novartis Investigative Site

Taichung, , Taiwan

Site Status RECRUITING

Novartis Investigative Site

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States Australia Austria Canada Czechia Hungary Poland Romania Singapore Slovakia South Korea Spain Taiwan

Central Contacts

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Novartis Pharmaceuticals

Role: CONTACT

1-888-669-6682

Novartis Pharmaceuticals

Role: CONTACT

+41613241111

Facility Contacts

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Casey Lewis

Role: primary

513-862-2877

Role: primary

615-343-6238

Other Identifiers

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2023-503452-27-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCTL019E2301

Identifier Type: -

Identifier Source: org_study_id

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