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.
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 Type
INTERVENTIONAL
Allocation
NA
25 mg oral lenalidomide once daily on Days 1-21 every 28 days
Cycle 1: 40 mg oral dexamethasone once daily on Days 8, 15, and 22. Cycle 2 and beyond: 40 mg oral dexamethasone once daily on Days 1, 8, 15, and 22
307 Hospital of Chinese PLA
Beijing, China
Peking University Third Hospital
Beijing, China
Peking Union Medical College Hospital
Beijing, China
Overall Response Rate
Complete Response (CR) or partial Response (PR) using the European Group for Blood and Marrow Transplantation (EBMT) (Bladé) criteria.
Time frame: Up to 24 months
Adverse Events
Number of participants with Adverse Events
Time frame: Up to 24 months
Progression Free Survival (PFS)
Number of participants who survive without progressing by the EBMT (Bladé) criteria
Time frame: Up to 24 months
Overall Survival
Number of participants alive
Time frame: Up to 24 months
Response duration
Length of time participants respond
Time frame: Up to 24 months
Maximum observed concentration in plasma
Pharmacokinetics - Cmax
Time frame: Days 1, 2, 7, 8, and 9 of Cycle 1
Area under the plasma concentration-time curve
Pharmacokinetics - AUC
Time frame: Days 1, 2, 7, 8, and 9 of Cycle 1
Time to maximum concentration
PK- Tmax
Time frame: Days 1, 2, 7, 8, and 9 of Cycle 1
Terminal half-life
Pharmacokinetics - T1/2
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Purpose
TREATMENT
Masking
NONE
Enrollment
194
Chinese PLA General Hospital
Beijing, China
Xiangya Hospital of Central- South University
Changsha, China
Guangdong General Hospital
Guangzhou, China
Nanfang Hospital of Southern Medical University
Guangzhou, China
The First Hospital Affiliated of College Medicine, Zhejiang University
Hangzhou, China
The First Hospital Affiliated of College Medicine, Zhejiang University
Hangzhou, China
Shanghai Changzheng Hospital
Shanghai, China
...and 3 more locations
Time frame: Days 1, 2, 7, 8, and 9 of Cycle 1
Apparent total body clearance
Pharmacokinetics - CL/F
Time frame: Days 1, 2, 7, 8, and 9 of Cycle 1
Apparent volume of distribution
Pharmacokinetics - Vz/F
Time frame: Days 1, 2, 7, 8, and 9 of Cycle 1