612 Participants Needed

Tazemetostat + Lenalidomide + Rituximab for Follicular Lymphoma

(SYMPHONY-1 Trial)

Recruiting at 249 trial locations
SA
CT
IR
IC
Overseen ByIpsen Clinical Study Enquiries
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Epizyme, Inc.
Must be taking: Lenalidomide
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

The participants of this study would have relapsed/refractory follicular lymphoma.Follicular lymphoma is a type of blood cancer. It is referred to as 'relapsed' when the disease has come back after a period of improvement after that follows a treatment regimen and 'refractory' when treatment no longer works.Stage 1 of this trial will study the safety and the level that adverse effects of each of the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for stage 2 and 3. Stage 1 of the study is completed.Stages 2 and 3 will evaluate and compare how long participants live without their disease getting worse when receiving the study drug in combination with other drug treatment versus the placebo (dummy drug) in combination with other drug treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take medications that are strong CYP3A inhibitors or inducers, and you should avoid grapefruit products. There are also specific time requirements between your last anticancer therapy and the start of the trial.

Is the combination of Tazemetostat, Lenalidomide, and Rituximab safe for treating follicular lymphoma?

Lenalidomide combined with Rituximab has shown an acceptable safety profile in treating follicular lymphoma, with manageable side effects like neutropenia (low white blood cell count) that can be controlled with dosage adjustments. Non-severe side effects such as fatigue and rash are generally manageable, and the combination is considered safe for use in humans.12345

What makes the drug combination of Tazemetostat, Lenalidomide, and Rituximab unique for treating follicular lymphoma?

This drug combination is unique because it includes Tazemetostat, which is an EZH2 inhibitor that targets specific genetic mutations in cancer cells, potentially enhancing the effectiveness of Lenalidomide and Rituximab, which are already known to be effective in treating follicular lymphoma. This combination aims to provide a more targeted approach to treatment, potentially improving outcomes for patients with this condition.16789

Who Is on the Research Team?

IM

Ipsen Medical Director

Principal Investigator

Ipsen

Are You a Good Fit for This Trial?

Adults with relapsed/refractory follicular lymphoma who've had prior treatments can join. They need good liver and kidney function, no major illnesses or brain metastases, not pregnant or breastfeeding, and must use effective contraception. Excluded are those with certain viral infections, recent major surgery, severe allergies to trial drugs, or taking specific medications.

Inclusion Criteria

I am a man who will use a condom or abstain from sex during and for 3 months after the study.
I had hepatitis but my liver functions are normal and my virus levels are undetectable.
All study participants enrolled must be registered into the mandatory Revlimid REMS™ program for the US or Revlimid Global PPP for ex-US and be willing and able to comply with the requirements of the Revlimid REMS™ or Revlimid Global PPP program as appropriate for the country in which the drug is being used
See 20 more

Exclusion Criteria

I have a serious heart condition.
I am currently being treated for an infection with medication.
I am not taking strong medications that affect liver enzymes or St. John's wort.
See 19 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Safety Run-in

Evaluate the safety and tolerability of tazemetostat and R2 combination, establish recommended dosage for subsequent stages

Completed

Stage 2: Efficacy and Safety

Assess efficacy and safety in patients with and without EZH2 mutation, includes interim analyses

Up to 96 months

Maintenance Therapy

Tazemetostat or placebo administered as monotherapy for up to 2 years after initial combination therapy

Up to 24 months

Stage 3: Long-term Follow-up

Monitor patients for response and overall survival, follow-up until 5 years post last patient enrollment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

  • Lenalidomide
  • Rituximab
  • Tazemetostat
Trial Overview The study tests Tazemetostat's effectiveness combined with Lenalidomide and Rituximab versus a placebo combination in improving survival without disease progression. Stage 1 focuses on safety and dosage; stages 2 and 3 compare the drug's efficacy against a placebo.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Tazemetostat + R2 armExperimental Treatment3 Interventions
Group II: Placebo + R2 ArmPlacebo Group3 Interventions

Lenalidomide is already approved in European Union, United States for the following indications:

🇪🇺
Approved in European Union as Revlimid for:
🇺🇸
Approved in United States as Revlimid for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Epizyme, Inc.

Lead Sponsor

Trials
34
Recruited
2,800+

Published Research Related to This Trial

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.
Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.
Lenalidomide: A Review in Previously Treated Follicular Lymphoma.Blair, HA.[2021]
In a study involving 263 patients with relapsed/refractory multiple myeloma, the ixazomib-lenalidomide-dexamethasone (IRd) combination showed a high overall response rate of 73% and a median progression-free survival of 21.2 months, indicating its effectiveness in routine clinical practice.
However, the treatment also had notable safety concerns, with 17% of patients requiring dose reductions for ixazomib and 36% for lenalidomide, and 32% of patients discontinuing ixazomib and 30% discontinuing lenalidomide due to adverse events.
Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma.Hájek, R., Minařík, J., Straub, J., et al.[2021]
Lenalidomide, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.
The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.
Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas.Ruan, J., Shah, B., Martin, P., et al.[2020]

Citations

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]
Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. [2021]
Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]
Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. [2021]
Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi. [2021]
Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). [2022]
Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. [2021]
Lenalidomide in follicular lymphoma. [2021]
Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. [2019]
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