A Multi-center, Open-Label Phase II Study to Determine the Efficacy and Safety of Lenalidomide Plus Low-Dose Dexamethasone in Chinese Subjects With Relapsed/Refractory Multiple Myeloma
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Celgene
- Enrollment
- 194
- Locations
- 12
- Primary Endpoint
- Overall Response Rate
Overview
Brief Summary
The purpose of this study is to determine the efficacy of lenalidomide plus low-dose dexamethasone in Chinese subjects with relapsed or refractory multiple myeloma.
Even though the efficacy and safety of lenalidomide has already been well-demonstrated in other populations including Asians, this study will assess the efficacy and safety as well as pharmacokinetics of lenalidomide in Chinese subjects. In addition, this study will generate clinically meaningful information in guiding the therapeutic use of lenalidomide for Chinese subjects.
Detailed Description
This is a Phase II, multicenter, single arm, open-label trial which will enroll Chinese subjects in China with relapsed/refractory multiple myeloma that will assess the efficacy and safety of lenalidomide plus low-dose dexamethasone regimen (Rd) given until progressive disease (PD) or discontinuation of lenalidomide for any reason.
There are two cohorts in this protocol, Pharmacokinetic Assessment Treatment Cohort and Treatment Cohort without Pharmacokinetic (PK) Assessment. The first 10 subjects who are ≤ 75 years old and have a baseline Creatinine Clearance ≥ 60 mL/min will participate in pharmacokinetic assessment during the first 8 days of Cycle 1. During this cohort, all subjects will receive 25mg oral lenalidomide once daily on days 1 -21 of each 28-day cycle. During the first cycle of this cohort, subjects will also receive 40mg oral dexamethasone daily on Days 8, 15, and 22 (and no dexamethasone on day 1). Beginning with Cycle 2, subjects will receive 25mg oral lenalidomide once daily on days 1 -21 of each 28-day cycle and 40mg oral dexamethasone daily on Days 1, 8, 15 and 22 of each 28-day cycle.
Once 10 subjects have been enrolled in the PK Assessment Treatment Cohort, the Treatment Cohort without PK Assessment will begin. During this cohort, subjects will receive lenalidomide 25 mg p.o. once daily on Days 1-21 and dexamethasone 40 mg p.o. once daily on Days 1, 8, 15, and 22 of each 28-day cycle. In both cohorts, subjects will continue Rd therapy until the documentation of PD or discontinuation of study therapy due to any reason including intolerable toxicity.
For the primary analysis, response will be assessed according to the European Group for Blood and Marrow Transplantation EBMT (Bladé) criteria by an Independent Response Adjudication Committee (IRAC). Response will also be assessed according to the International Myeloma Working Group (IMWG) criteria and used as an exploratory analysis.
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
- •Understand and voluntarily sign informed consent form
- •Age ≥ 18 years at the time of signing consent
- •Prior or current diagnosis of Durie-Salmon Stage II or III multiple myeloma AND have disease progression after at least 2 cycles of systemic anti-myeloma treatment or have relapsed with progressive disease after treatment.
- •Measurable levels of myeloma paraprotein in serum (≥ 0.5 g/dL \[5 g/L\] or urine (≥ 0.2 g excreted in a 24-hour collection sample).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Must agree to comply to Lenalidomide Pregnancy Prevention Risk Management Plan requirements.
- •Exclusion Criteria
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Subjects with non-secretory multiple myeloma by Serum Protein Electrophoresis (SPEP) and Urine Protein Electrophoresis (UPEP) assessment.
Exclusion Criteria
- Not provided
Arms & Interventions
Lenalidomide and dexamethasone
Cycle 1: 25 mg oral lenalidomide once daily on Days 1-21 every 28 Days and 40 mg oral dexamethasone on Days 8, 15, and 22. Cycle 2 and beyond: 25 oral lenalidomide once daily on Days 1-21 every 28 days and 40 mg oral dexamethasone once daily on Days 1, 8, 15, and 22.
Intervention: Lenalidomide (Drug)
Lenalidomide and dexamethasone
Cycle 1: 25 mg oral lenalidomide once daily on Days 1-21 every 28 Days and 40 mg oral dexamethasone on Days 8, 15, and 22. Cycle 2 and beyond: 25 oral lenalidomide once daily on Days 1-21 every 28 days and 40 mg oral dexamethasone once daily on Days 1, 8, 15, and 22.
Intervention: Dexamethasone (Drug)
Outcomes
Primary Outcomes
Overall Response Rate
Time Frame: Up to 24 months
Complete Response (CR) or partial Response (PR) using the European Group for Blood and Marrow Transplantation (EBMT) (Bladé) criteria.
Secondary Outcomes
- Progression Free Survival (PFS)(Up to 24 months)
- Terminal half-life(Days 1, 2, 7, 8, and 9 of Cycle 1)
- Apparent volume of distribution(Days 1, 2, 7, 8, and 9 of Cycle 1)
- Adverse Events(Up to 24 months)
- Area under the plasma concentration-time curve(Days 1, 2, 7, 8, and 9 of Cycle 1)
- Time to maximum concentration(Days 1, 2, 7, 8, and 9 of Cycle 1)
- Overall Survival(Up to 24 months)
- Response duration(Up to 24 months)
- Maximum observed concentration in plasma(Days 1, 2, 7, 8, and 9 of Cycle 1)
- Apparent total body clearance(Days 1, 2, 7, 8, and 9 of Cycle 1)