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

Overview

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

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.

Eligibility

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