A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
- Conditions
- Follicular Lymphoma (FL)
- Interventions
- Drug: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cyclesDrug: Lymphodepleting chemotherapyOther: Corticosteroids and/or Radiation (Bridging therapy)
- Registration Number
- NCT05888493
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 108
- 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.
- 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.
Other protocol defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R2 or R-CHOP Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles 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. Tisagenlecleucel 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 Tisagenlecleucel Corticosteroids and/or Radiation (Bridging therapy) 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 R2 or R-CHOP Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles. 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. Tisagenlecleucel Lymphodepleting chemotherapy 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
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) determined by blinded independent review committee (BIRC) 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
- Secondary Outcome Measures
Name Time Method Overall survival (OS) 5 years OS: Time from randomization to date of death due to any cause
Time to next anti-lymphoma treatment (TTNT) 5 years TTNT: Time from randomization until start of new anticancer therapy or death due to any cause.
Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity) 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.
Duration of Response (DOR) 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
Complete response rate (CRR) as assessed by BIRC (Key Secondary) 5 years CRR: The proportion of participants with BOR of complete response (CR)
Overall response rate (ORR) by BIRC 5 years ORR: The proportion of participants with BOR of either CR or partial response (PR)
Anti-mCAR, T cell response, as measured by IFNγ expression (cellular immunogenicity) 5 years Summarize cellular immunogenicity by pre-infusion and post-infusion timepoints, and correlate cellular immunogenicity signals with CAR expansion, efficacy, and safety endpoints.
CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available) 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.
Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel 5 years This is to assess presence of (Replication competent lentivirus) RCL in participants receiving tisagenlecleucel by VSV-g qPCR
Trial Locations
- Locations (2)
TRIHEALTH Good Samarithan Hospital
🇺🇸Cincinnati, Ohio, United States
Novartis Investigative Site
🇨🇳Taipei, Taiwan