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

NCT05888493 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CCTL019E23012023-503452-27-00
• Study Type: interventional
• Target: 109
• Locations: 10 countries
• Sites: 29

Brief Summary

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

Conditions

Follicular Lymphoma (FL)

Keywords

relapsed or refractory follicular lymphoma; r/r; FL; CAR-T; tisagenlecleucel; CTL019; phase III; standard of care; SOC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) determined by blinded independent review committee (BIRC)

  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 Outcomes (8)

• Complete response rate (CRR) as assessed by BIRC (Key Secondary)

  5 years

• Overall response rate (ORR) by BIRC

  5 years

• Overall survival (OS)

  5 years

• Time to next anti-lymphoma treatment (TTNT)

  5 years

• Duration of Response (DOR)

  5 years

Study Arms (2)

Tisagenlecleucel

EXPERIMENTAL

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; Drug: Lymphodepleting chemotherapy; Other: Corticosteroids and/or Radiation (Bridging therapy)

R2 or R-CHOP

ACTIVE COMPARATOR

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

Interventions

Tisagenlecleucel BIOLOGICAL

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

Also known as: CTL019

Tisagenlecleucel

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

Also known as: R2

R2 or R-CHOP

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

Also known as: R-CHOP

R2 or R-CHOP

Lymphodepleting chemotherapy 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)

Tisagenlecleucel

Corticosteroids and/or Radiation (Bridging therapy) OTHER

Corticosteroids and/or Radiation

Tisagenlecleucel

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the date of signing the informed consent form.
• Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).
• Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.
• 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.
• ECOG performance status of 0, 1 or 2 at screening.
• Adequate hematologic, renal, hepatic and pulmonary organ function at screening.
• Must meet the institutional criteria to undergo leukapheresis (unless historical leukapheresis is available).
• Must be eligible for treatment with the selected standard of care regimen.

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (30)

Novartis Investigative Site

Camperdown, New South Wales, 2050, Australia

Location

Novartis Investigative Site

Clayton, Victoria, 3168, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Ostrava, Poruba, 708 52, Czechia

Location

Novartis Investigative Site

Budapest, H-1097, Hungary

Location

Novartis Investigative Site

Poznan, Greater Poland Voivodeship, 60-355, Poland

Location

Novartis Investigative Site

Gliwice, Silesian Voivodeship, 44-101, Poland

Location

Novartis Investigative Site

Gdansk, 80-952, Poland

Location

Novartis Investigative Site

Lodz, 93-513, Poland

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Bratislava, 83310, Slovakia

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Seoul, 06591, South Korea

Location

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Santander, Cantabria, 39008, Spain

Location

Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Córdoba, 14004, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Salamanca, 37007, Spain

Location

Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

Location

Novartis Investigative Site

Taichung, 407219, Taiwan

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Recurrence

Interventions

tisagenlecleucel; Lenalidomide; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Prednisolone; R-CHOP protocol

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 1, 2023
• First Posted: June 5, 2023
• Study Start: October 2, 2023
• Primary Completion (Estimated): July 25, 2028
• Study Completion (Estimated): February 20, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CZ (1); HU (1); SG (1); SL (1); KR (5); TW (3); AU (4); CA (1); PL (4); ES (8)