A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.
Study details:
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 criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT05888493
Intervention or treatment
BIOLOGICAL: Tisagenlecleucel
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
DRUG: Lymphodepleting chemotherapy
OTHER: Corticosteroids and/or Radiation (Bridging therapy)
Conditions
- Follicular Lymphoma (FL)
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Research sites nearby
Closest Location:
Novartis Investigative Site
Select from list below to view details:
Novartis Investigative Site
Camperdown, New South Wales, Australia
Novartis Investigative Site
Clayton, Victoria, Australia
Novartis Investigative Site
Melbourne, Victoria, Australia
Novartis Investigative Site
Nedlands, Western Australia, Australia
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Who is running the clinical trial?
Novartis Pharmaceuticals
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?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Tisagenlecleucel
| Biological: Tisagenlecleucel, Drug: Lymphodepleting chemotherapy, Other: Corticosteroids and/or Radiation (Bridging therapy) |
ACTIVE_COMPARATOR: R2 or R-CHOP
| 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 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Complete response rate (CRR) as assessed by BIRC (Key Secondary) | CRR: The proportion of participants with BOR of complete response (CR) | 5 years |
| Overall response rate (ORR) by BIRC | ORR: The proportion of participants with BOR of either CR or partial response (PR) | 5 years |
| Overall survival (OS) | OS: Time from randomization to date of death due to any cause | 5 years |
| Time to next anti-lymphoma treatment (TTNT) | TTNT: Time from randomization until start of new anticancer therapy or death due to any cause. | 5 years |
| Duration of Response (DOR) | 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) | 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) | 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) | 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 | This is to assess presence of (Replication competent lentivirus) RCL in participants receiving tisagenlecleucel by VSV-g qPCR | 5 years |
References
Clinical Trials Gov: A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular LymphomaOther trials to consider
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