A Phase 2, Multicenter, Single-Arm, Open-Label Study To Determine The Efficacy And Safety Of Single-Agent Lenalidomide (Revlimid®) In Patients With Mantel Cell NHL Who Have Relapsed Or Progressed After Treatment With Bortezomib Or Are Refractory To Bortezomib
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Celgene
- Enrollment
- 134
- Locations
- 70
- Primary Endpoint
- Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC)
Overview
Brief Summary
To evaluate the safety and efficacy of Lenalidomide (Revlimid (R)) in subjects with mantle cell lymphoma who have relapsed, progressed or are refractory to bortezomib.
Detailed Description
Follow up phase will continue until either 100% of the patients have died, are lost to follow up or have withdrawn consent or a maximum of 4 years from the last patient enrolled, whichever comes first. All other efficacy and safety endpoints will be updated at this time. In the unlikely event that the study will be closed and patients are still responding to treatment at this time, Celgene will discuss with the treating physicians options to provide further treatment to the patient after study closure in line with local regulation.
Follow up for second primary malignancies and OS will continue until 100% of the patients have died, are lost to follow up, have withdrawn consent, or a maximum of 5 years from the last patient enrolled, whichever comes first.
10 October 2017: In regard to the last subject last visit date/study completion date, the prolongation of timelines is due to the bridging of a treatment gap for a patient responding to study medication until non-study medication is available.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Biopsy proven mantle cell lymphoma
- •Patients must have documents relapsed, refractory or PD after treatment with bortezomib
- •Must have measureable disease on cross sectional imaging by CT
- •Eastern Cooperative Oncology Group (ECOG) performance score 0,1 or 2
- •Willing to follow pregnancy precautions
Exclusion Criteria
- •Any of the following laboratory abnormalities
- •Absolute neutrophil count (ANC) \< 1,500 cells/mm3 (1.5 x 109/L)
- •Platelet count \< 60,000/mm3 (60 x 109/L)
- •Serum aspartate transaminase/Serum glutamic oxaloacetic transaminase(AST/SGOT) or alanine transaminase/Serum glutamic pyruvic transaminase (ALT/SGPT) \> 3.0 x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma.
- •Serum total bilirubin \> 1.5 x ULN, except in cases of Gilbert's Syndrome and documented liver involvement by lymphoma.
- •Calculated creatinine clearance (Cockcroft-Gault formula) of \< 30 mL /min
- •Patients who are candidates for high dose chemotherapy/allogeneic stem cell transplant are not eligible
- •History of active central nervous system (CNS) lymphoma within the previous 3 months
- •Subjects not willing or unable to take deep vein thrombosis (DVT) prophylaxis
- •Prior history of malignancies, other than MCL, unless the patient has been free of the disease for ≥ 3 years
Arms & Interventions
Lenalidomide
Single agent Lenalidomide
Lenalidomide: 10mg or 25 mg oral capsules on days 1 to 21 of each 28 day cycle and dependent on renal function; Participants with normal renal function (defined as Creatinine Clearance(CrCl)) of ≥ 60 mL/min in this study) received 25 mg of lenalidomide daily, and those with moderate renal insufficiency (CrCl) ≥ 30 mL/min but < 60 mL/min) were started at a 10-mg dose. Participants could continue to receive treatment until disease progression, development of unacceptable AEs, or voluntary withdrawal.
Intervention: lenalidomide (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Who Achieved an Overall Response According to the Independent Review Committee (IRC)
Time Frame: From Day 1 of study treatment to progession or early treatment discontinuation; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days.
Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed, or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 75% in the SPD compared with original mass; 2) indeterminate bone marrow; PR = is defined ≥50% decrease in 6 largest nodes or nodal masses.
Kaplan Meier Estimate of Duration of Response (DoR) According to the Independent Review Committee
Time Frame: From Day 1 of study drug to progression or early treatment discontinuation; up to data cut-off date of 06 April 2016; Median duration of treatment was 94.5 days.
Kaplan Meier estimate for the duration of response (DoR) was calculated from the date of the first occurrence of initial response for responders (demonstrating evidence of at least a PR) to the date of first documented disease progression (any new lesion or increase by ≥ 50% of previously involved sites from nadir) or death (without documented progression) for participants who responded; participants who had not progressed (or died) were censored at the last valid assessment.
Secondary Outcomes
- Percentage of Participants With a Complete Response (CR) /Complete Response Unconfirmed (CRu) According to the Independent Review Committee(From Day 1 of study drug to progression or early treatment discontinuation; up to data cut-off date of 06 April 2016; Median duration of treatment was 94.5 days)
- Kaplan Meier Estimate of Duration of Complete Response (DoCR) (CR+CRu) According to the Independent Review Committee(From Day 1 of study drug to progression or early discontinuation; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months)
- Kaplan-Meier Estimate of Progression-Free Survival (PFS) According to the Independent Review Committee(From Day 1 of study drug to first documented date of disease progression; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months)
- Kaplan Meier Estimate of Time to Progression (TTP) According to the Independent Review Committee(From Day 1 of study drug to first documented time of progression; up to data cut-off date of 06 April 2016; median time in follow-up was 16.34 months)
- Kaplan-Meier Estimate of Time to Treatment Failure (TTF) According to the Independent Review Committee(From Day 1 of study drug to first documented time of treatment failure; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days)
- Time to Response (TTR)(From Day 1 of study drug to time of first documented PR or better; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days)
- Time to Complete Response (CR+CRu) According to the Independent Review Committee(From Day 1 of study drug to first documented CR/CRu or better; up to data cut-off date of 06 April 2016; median duration of treatment was 94.5 days)
- Overall Survival (OS)(From Day 1 of study drug to first documented date of progressive disease or death; up to the final data cut-off date of 30 March 2017; median duration of follow-up for surviving participants was 62.94 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From the first dose of lenalidomide through 28 days after the last dose during the follow-up phase; median (minimum, maximum) duration of treatment was 94.0 (1.0, 1950 days))