cc-5013-nhl-008

Bristol-Myers Squibb

Chaussee de la Hulpe 185, Brussels, Belgium, 1170

Global Submission Management - Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, mg-gsm-ct@bms.com

No

No

Final

30 Sep 2024

No

Yes

17 Sep 2024

No

The primary objective of the study is to compare the efficacy of lenalidomide plus rituximab combination maintenance therapy (for 18 cycles) followed by optional lenalidomide single-agent maintenance (to progression) versus rituximab single-agent maintenance (for 18 cycles) after 12 cycles of induction therapy with lenalidomide plus rituximab, in subjects with relapsed/refractory FL grades 1-3b, transformed FL, MZL or MCL. Efficacy determinations will be based upon PFS as the primary endpoint, using a modification of the IWG 1999 criteria.

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

01 Apr 2014

No

Yes

United States: 459

Germany: 44

503

44

0

0

0

0

0

0

209

240

54

Induction Period

Randomised - controlled

Rituximab

Concentrate and solvent for solution for injection/infusion

Intravenous use

Rituximab 375 mg/m2 every week in Cycle 1 (Days 1, 8, 15, and 22) and Day 1 of every 28-day Cycle for Cycles 3, 5, 7, 9, and 11

Lenalidomide

Capsule

Oral use

Lenalidomide 20 mg 10 mg if creatinine clearance ≥ 30 mL/min but < 60 mL/min) once daily on Days 1 to 21 of every 28-day Cycle for Cycles 1 to 12

Maintenance Period

Randomised - controlled

Yes

Rituximab

Concentrate and solvent for solution for injection/infusion

Intravenous use

Rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29.

Lenalidomide

Capsule

Oral use

18 Cycles: lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle for Cycles 13 to 30. Followed by Optional Maintenance Period (up to PD): Lenalidomide 10 mg once daily on Days 1 to 21 of every 28-day Cycle up to PD.

Rituximab

Concentrate and solvent for solution for injection/infusion

Intravenous use

18 Cycles: rituximab 375 mg/m2 on Day 1 of every 28-day Cycle for Cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29

Induction Period

Induction Period: Lenalidomide - Rituximab

Arm A: Lenalidomide + Rituximab

Arm B: Rituximab

Progression free survival (PFS) is defined as the time from the date of first dose of maintenance therapy to the date of the first objective documentation of tumor progression or death due to any cause. Analysis was based on Kaplan Meier estimates. The PFS events were determined using a modification of the IWG 1999 criteria.

Primary

From the first dose date of maintenance therapy to objective disease progression or death from any cause, whichever occurs first (up to approximately 432 weeks)

Arm A: Lenalidomide + Rituximab v Arm B: Rituximab

267

Pre-specified

0.8

2-sided

Overall Survival (OS) is defined as the time between the first dose date of maintenance therapy and death from any cause. Participants who complete the study and are still alive at the time of the clinical data cutoff date will be censored at the last visit date or the last contact date, whichever is later. Participants who were lost to follow-up prior to the clinical data cut-off date will also be censored at the time of the last contact. Analysis was based on Kaplan Meier estimates and Hazard Ratio (HR). "99999"=N/A

Secondary

From the first dose date of maintenance therapy to death from any cause (up to approximately 480 weeks)

Arm A: Lenalidomide + Rituximab v Arm B: Rituximab

267

Pre-specified

0.7

2-sided

Improvement of Response (IOR) is the percentage of participants with improved tumor response during the maintenance phase (converted from partial response at end of induction to complete response or complete response unconfirmed as best response) and participants who converted from stable disease at the end of induction period to partial response or better as best response during maintenance phase.

Secondary

From the first dose date of maintenance therapy to death from any cause (up to approximately 432 weeks)

The overall response rate (ORR) is defined as the percentage of participants with a best response of at least PR (including CR, CRu and PR) after the first dose date of maintenance therapy and prior to any treatment change.

Secondary

From the first dose date of maintenance therapy up to CR, CRu, PR, or treatment change (up to approximately 432 weeks)

Best Complete Response Rate (CRR), defined as the proportion of participants with a best response of at least CRu (including CR and CRu) after the first dose date of maintenance therapy and prior to any treatment change.

Secondary

From the first dose date of maintenance therapy up to CR or CRu (up to approximately 432 weeks)

DOR is from initial response (at least CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death. Participants who have not progressed or died at the time of the clinical data cutoff date will be censored at the last assessment showing no progression. Participants who change treatment without evidence of disease progression will be censored at the last assessment showing no progression prior to treatment change. Analysis was based on Kaplan Meier estimates. "99999"=N/A

Secondary

From the initial response (at least PR) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)

Time to next anti-lymphoma treatment is defined as the time from the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy. Participants without new treatment therapy will be censored at the last visit. Analysis was based on Kaplan Meier estimates. "99999"=N/A

Secondary

From the first dose date of maintenance therapy to the time of first documented administration of new anti-lymphoma therapy (up to approximately 300 weeks)

Time to histological transformation is defined as from the first dose date of maintenance therapy to the time of histological transformation as measured based on documentation of histological transformation (as assessed by the investigator). Analysis was based on Kaplan Meier estimates. In case of clinical suspicion of transformation, including rapid disease progression, unexpected changes in “B” symptoms or rapidly increasing LDH, a biopsy should be performed. In this clinical trial, histological transformation will be considered disease progression. This endpoint will not be calculated for participants randomized with transformed Follicular Lymphoma (tFL). "99999"=N/A

Secondary

From the first dose date of maintenance therapy to the time of histological transformation (up to approximately 432 weeks)

Duration of complete response (DOCR) is calculated as the time from the initial response (CR or CRu) after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death. Analysis was based on Kaplan Meier estimates. Participants who have not progressed or died at the time of the clinical data cutoff date will be censored at the last assessment showing no progression. Participants who change treatment without evidence of disease progression will be censored at the last assessment showing no progression prior to treatment change. "99999"=N/A

Secondary

From the initial CR/CRu after the first dose date of maintenance therapy and prior to treatment change to documented disease progression or death, whichever occurs first (up to approximately 432 weeks)

Number of participants experiencing AEs, SAEs, AEs leading to study discontinuation, and AEs of interest (AEIs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. SAEs is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization; results significant disability; or is a congenital anomaly/birth defect. TEAEs are defined as AEs with an onset date on or after the first dose of study treatment up to 30 days after the last dose of study treatment in the study, or if a pre-existing condition worsens in severity or becomes serious after receiving the first dose of study treatment.

Secondary

From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

The number of participants who experienced adverse events related to vital sign measurements.

Secondary

From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Clinical laboratory values in induction period include any laboratory values that are taken after the first dose date of induction therapy through 28 days after the last dose date of induction therapy or before the first dose date of maintenance therapy, whichever is earlier. Graded according to the NCI CTCAE version 4.03, except for tumor flare reaction, which is accessed using NCI CTCAE version 3.0. Participants with zero maximum grade are excluded.

Secondary

From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

Clinical laboratory values in induction period include any laboratory values that are taken after the first dose date of induction therapy through 28 days after the last dose date of therapy. Graded according to the NCI CTCAE version 4.03, except for tumor flare reaction, which is accessed using NCI CTCAE version 3.0. Participants with zero maximum grade are excluded.

Secondary

From first dose up to 30 days after last dose (up to approximately 64 weeks for induction period and 427 weeks for maintenance period)

All-cause mortality was assessed from first dose to study completion (up to approx. 10 years). SAEs & AEs were assessed from first dose to 30 days following last dose (up to approx. 64 weeks for induction period & 427 weeks for maintenance period).

26.1

Induction Period: Lenalidomide - Rituximab

Maintenance Period: Arm A

Maintenance Period: Arm B