← Back to Search

Immunomodulatory agent

Tazemetostat + Lenalidomide + Rituximab for Follicular Lymphoma (SYMPHONY-1 Trial)

Phase 3

Recruiting

Research Sponsored by Epizyme, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Males or females are ≥18 years of age (≥20 years for Taiwan) at the time of providing voluntary written informed consent.

Adequate renal function defined as calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula

Must not have

Significant cardiovascular impairment

Have an active infection requiring systemic therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up stage 2: up to 96 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new combination drug to treat people with a certain type of lymphoma who have not responded to other treatments. The trial will use biomarkers to select patients most likely to benefit from the new drug.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include liver issues due to medication interactions, digestive problems that could affect drug absorption, blood disorders like anemia or clotting issues from bone marrow suppression, allergic reactions to the drugs used in treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am at least 18 years old, or 20 if I'm from Taiwan, and can give consent.

Select...

My kidneys work well enough, with a creatinine clearance rate of at least 30 mL/min.

Select...

I have had at least one treatment with chemotherapy, immunotherapy, or both.

Select...

I have waited the required time after my last cancer treatment before starting tazemetostat.

Select...

My cancer returned or didn't respond well to treatment.

Select...

All my previous cancer treatment side effects are mild or stable now.

Select...

I am using two reliable birth control methods or practicing abstinence.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Select...

My lymphoma is confirmed to be Follicular Lymphoma, Grades 1 to 3A.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a serious heart condition.

Select...

I am currently being treated for an infection with medication.

Select...

I am not taking strong medications that affect liver enzymes or St. John's wort.

Select...

I have a cancer type other than follicular lymphoma.

Select...

I have previously been treated with tazemetostat or similar medications.

Select...

I have or had brain metastases that are not currently under control.

Select...

I am not pregnant or breastfeeding.

Select...

I cannot take medication to prevent Pneumocystis pneumonia.

Select...

I have had a solid organ transplant.

Select...

I have severe blood cell count issues or a history of certain blood cancers.

Select...

I have been treated with lenalidomide before.

Select...

I have an active infection with hepatitis C, HIV, or HTLV-1.

Select...

My heart's electrical activity test shows a prolonged QT interval.

Select...

I have a history of T-cell lymphoblastic lymphoma or leukemia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ stage 2: up to 96 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~stage 2: up to 96 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and stage 2: up to 96 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

PFS in the Intent-to-treat mutant-type (ITT-MT) population

Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) population

Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2)

Secondary study objectives

CRR in ITT-MT population

CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status

Complete Response Rate (CRR) in ITT-WT population

+22 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Tazemetostat + R2 armExperimental Treatment3 Interventions

Stage 1 (Phase 1b): This phase is now completed. * Tazemetostat was escalated from a starting dose of 400 mg PO twice daily to 600 mg PO twice daily to 800 mg PO twice daily in 28-day cycles. * Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. * Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administred PO QD on days 1 to 21 for 12 cycles. Stage 2: * Tazemetostat 800 mg administered PO twice daily in continuous 28-day cycles. * Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. * Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), PO QD on days 1 to 21 for 12 cycles. Maintenance Therapy (Stages 1 and 2): Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy.

Group II: Placebo + R2 ArmPlacebo Group3 Interventions

Stage 2: * Placebo administered PO twice daily in continuous 28-day cycles. * Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5. * Lenalidomide 20 mg or 10 mg (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles. Maintenance Therapy (Stage 2): Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. During maintenance, placebo will be continued until disease progression or unacceptable toxicity, or participant withdraws consent.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tazemetostat

2016

Completed Phase 2

~1050

Lenalidomide

2005

Completed Phase 3

~2240