A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.

Conditions

• Follicular Lymphoma
• Refractory Follicular Lymphoma
• Relapsed/Refractory Follicular Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Tazemetostat — DRUG
  Stage 1 (Phase 1b): Tazemetostat was escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. 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. Following implementation of the urgent safety measure, tazemetostat administration was discontinued. No further dosing is performed.
• Tazemetostat — DRUG
  Stage 2: Tazemetostat 800 mg administered orally twice daily in continuous 28-day cycles for 12 cycles. 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.
• Placebo oral tablet — DRUG
  Stage 2: Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. Following implementation of the urgent safety measure, placebo administration was discontinued.
• Lenalidomide — COMBINATION_PRODUCT
  Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.
• Rituximab — COMBINATION_PRODUCT
  Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.

Study Details

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 studied 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 were designed to 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. However, following an urgent safety measure, treatment with tazemetostat and placebo was discontinued, enrollment was stopped, and the study was unblinded. As a result, post-urgent safety measure analyses are descriptive in nature.

Key Dates

First listed

Jan 13, 2020

Start date

Jun 11, 2020

Status verified

Aug 2026

Primary completion

Feb 13, 2027

Completion

Mar 1, 2029

Study Design

Enrollment

599 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Tazemetostat + R2 arm
  Stage 1 (Phase 1b): completed * Tazemetostat escalated 400mg PO twice daily to 600mg PO twice daily (BD) to 800mg PO BD in 28-day cycles * Rituximab 375mg/m2 IV on days 1, 8, 15, \& 22 of cycle 1; then on day 1 of cycles 2-5 * Lenalidomide 20mg or 10mg, administered PO QD on days 1-21 for 12 cycles Stage 2: * Tazemetostat 800mg administered PO BD in continuous 28-day cycles. * Rituximab 375mg/m2 IV on days 1, 8, 15, \& 22 of cycle 1; then on day 1 of cycles 2-5 * Lenalidomide 20mg or 10mg, administered PO QD on days 1-21 for 12 cycles Maintenance Therapy (Stages 1\&2): Tazemetostat 800mg PO BD dose for up to 2 years after the initial 12 months of combination therapy. Following an Independent Data Monitoring Committee review, an urgent safety measure was implemented and administration of tazemetostat was permanently discontinued. No further investigational treatment is administered. Participants previously exposed to tazemetostat enter protocol-specified long-term safety follow-up
• Placebo Comparator: Placebo + R2 Arm
  Participants were assigned to receive placebo in combination with lenalidomide and rituximab. Following implementation of the urgent safety measure, placebo administration was permanently discontinued. No further investigational treatment is administered. 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.

Primary Outcome Measure

Phase 1b: Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2) [ Time Frame: Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 was selected at the end of Stage 1 ]

Locations (57)

Find similar trials in Mobile, AL

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