Study of Lenalidomide and Low-Dose Dexamethasone in Chinese Subjects With Relapsed/Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Lenalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Efficacy/Safety, Lenalidomide and Low-Dose Dexamethasone, Chinese Subjects, Relapsed/Refractory Multiple Myeloma
Eligibility Criteria
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 2.
- 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.
- Pregnant or lactating females
Any of the following laboratory abnormalities:
- Absolute neutrophil count of < 1000 cells/mm3 (1.0 X 109/L)
- Platelet count < 50,000/mm3 (50 X 109/L) in subjects in whom < 50% of the bone marrow nucleated cells were plasma cells
- Renal failure requiring dialysis or peritoneal dialysis
- Serum glutamic oxaloacetic transaminase, (SGOT)/ Aspartate-Aminotransferase (AST) > 3.0 x upper limit of normal (ULN)
- Serum total bilirubin > 2.0 mg/dL (34μmol/L)
- Any condition, including the presence of laboratory abnormalities, which placed subject at unacceptable risk if participating in the study or which would confound the ability to interpret study data.
- Significant active cardiac disease within the previous 6 months.
Prior history of malignancies, other than multiple myeloma, unless the subject has been free of disease for ≥ 3 years. Exceptions include the following:
- Basal cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Squamous cell carcinoma of the skin
- Incidental histologic finding of prostate cancer (Tumor, Node, and Metastasis [TNM] stage of T1a or T1b)
- Known hypersensitivity to thalidomide or dexamethasone
- Prior history of uncontrollable side effects to dexamethasone therapy
- Peripheral neuropathy ≥ grade 2
- Prior use of lenalidomide
- Use of any standard/experimental anti-myeloma drug therapy within 28 days of the start of study drug or use of any experimental non-drug therapy (e.g. donor leukocyte/mononuclear cell infusion) within 56 days of the start of study drug)
- Unable or unwilling to undergo antithrombotic therapy
- History of deep vein thrombosis (DVT) or pulmonary emboli (PE) within the past 12 months
- Known HIV positivity
- Active infectious hepatitis A, B, or C or chronic carriers of hepatitis B with hepatitis B surface antigen (HBsAG) positive or if the hepatitis B viral deoxyribonucleic acid (HBV DNA) level is detectable by polymerase chain reaction (PCR).
Sites / Locations
- 307 Hospital of Chinese PLA
- Peking University Third Hospital
- Peking Union Medical College Hospital
- Chinese PLA General Hospital
- Xiangya Hospital of Central- South University
- Guangdong General Hospital
- Nanfang Hospital of Southern Medical University
- The First Hospital Affiliated of College Medicine, Zhejiang University
- The First Hospital Affiliated of College Medicine, Zhejiang University
- Shanghai Changzheng Hospital
- Shanghai 6th People's Hospital
- Changhai Hospital
- The First Affiliated Hospital of Soochow University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Lenalidomide and dexamethasone
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall Response Rate
Complete Response (CR) or partial Response (PR) using the European Group for Blood and Marrow Transplantation (EBMT) (Bladé) criteria.
Secondary Outcome Measures
Adverse Events
Number of participants with Adverse Events
Progression Free Survival (PFS)
Number of participants who survive without progressing by the EBMT (Bladé) criteria
Overall Survival
Number of participants alive
Response duration
Length of time participants respond
Maximum observed concentration in plasma
Pharmacokinetics - Cmax
Area under the plasma concentration-time curve
Pharmacokinetics - AUC
Time to maximum concentration
PK- Tmax
Terminal half-life
Pharmacokinetics - T1/2
Apparent total body clearance
Pharmacokinetics - CL/F
Apparent volume of distribution
Pharmacokinetics - Vz/F
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01593410
Brief Title
Study of Lenalidomide and Low-Dose Dexamethasone in Chinese Subjects With Relapsed/Refractory Multiple Myeloma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 1, 2010 (Actual)
Primary Completion Date
January 3, 2013 (Actual)
Study Completion Date
January 3, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Efficacy/Safety, Lenalidomide and Low-Dose Dexamethasone, Chinese Subjects, Relapsed/Refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
194 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lenalidomide and dexamethasone
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
25 mg oral lenalidomide once daily on Days 1-21 every 28 days
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
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
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
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
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Number of participants with Adverse Events
Time Frame
Up to 24 months
Title
Progression Free Survival (PFS)
Description
Number of participants who survive without progressing by the EBMT (Bladé) criteria
Time Frame
Up to 24 months
Title
Overall Survival
Description
Number of participants alive
Time Frame
Up to 24 months
Title
Response duration
Description
Length of time participants respond
Time Frame
Up to 24 months
Title
Maximum observed concentration in plasma
Description
Pharmacokinetics - Cmax
Time Frame
Days 1, 2, 7, 8, and 9 of Cycle 1
Title
Area under the plasma concentration-time curve
Description
Pharmacokinetics - AUC
Time Frame
Days 1, 2, 7, 8, and 9 of Cycle 1
Title
Time to maximum concentration
Description
PK- Tmax
Time Frame
Days 1, 2, 7, 8, and 9 of Cycle 1
Title
Terminal half-life
Description
Pharmacokinetics - T1/2
Time Frame
Days 1, 2, 7, 8, and 9 of Cycle 1
Title
Apparent total body clearance
Description
Pharmacokinetics - CL/F
Time Frame
Days 1, 2, 7, 8, and 9 of Cycle 1
Title
Apparent volume of distribution
Description
Pharmacokinetics - Vz/F
Time Frame
Days 1, 2, 7, 8, and 9 of Cycle 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 2.
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.
Pregnant or lactating females
Any of the following laboratory abnormalities:
Absolute neutrophil count of < 1000 cells/mm3 (1.0 X 109/L)
Platelet count < 50,000/mm3 (50 X 109/L) in subjects in whom < 50% of the bone marrow nucleated cells were plasma cells
Renal failure requiring dialysis or peritoneal dialysis
Serum glutamic oxaloacetic transaminase, (SGOT)/ Aspartate-Aminotransferase (AST) > 3.0 x upper limit of normal (ULN)
Serum total bilirubin > 2.0 mg/dL (34μmol/L)
Any condition, including the presence of laboratory abnormalities, which placed subject at unacceptable risk if participating in the study or which would confound the ability to interpret study data.
Significant active cardiac disease within the previous 6 months.
Prior history of malignancies, other than multiple myeloma, unless the subject has been free of disease for ≥ 3 years. Exceptions include the following:
Basal cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Squamous cell carcinoma of the skin
Incidental histologic finding of prostate cancer (Tumor, Node, and Metastasis [TNM] stage of T1a or T1b)
Known hypersensitivity to thalidomide or dexamethasone
Prior history of uncontrollable side effects to dexamethasone therapy
Peripheral neuropathy ≥ grade 2
Prior use of lenalidomide
Use of any standard/experimental anti-myeloma drug therapy within 28 days of the start of study drug or use of any experimental non-drug therapy (e.g. donor leukocyte/mononuclear cell infusion) within 56 days of the start of study drug)
Unable or unwilling to undergo antithrombotic therapy
History of deep vein thrombosis (DVT) or pulmonary emboli (PE) within the past 12 months
Known HIV positivity
Active infectious hepatitis A, B, or C or chronic carriers of hepatitis B with hepatitis B surface antigen (HBsAG) positive or if the hepatitis B viral deoxyribonucleic acid (HBV DNA) level is detectable by polymerase chain reaction (PCR).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jay Mei, M.D.
Organizational Affiliation
Celgene
Official's Role
Study Director
Facility Information:
Facility Name
307 Hospital of Chinese PLA
City
Beijing
ZIP/Postal Code
100071
Country
China
Facility Name
Peking University Third Hospital
City
Beijing
ZIP/Postal Code
100081
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Chinese PLA General Hospital
City
Beijing
ZIP/Postal Code
300200
Country
China
Facility Name
Xiangya Hospital of Central- South University
City
Changsha
ZIP/Postal Code
410008
Country
China
Facility Name
Guangdong General Hospital
City
Guangzhou
ZIP/Postal Code
510080
Country
China
Facility Name
Nanfang Hospital of Southern Medical University
City
Guangzhou
ZIP/Postal Code
510515
Country
China
Facility Name
The First Hospital Affiliated of College Medicine, Zhejiang University
City
Hangzhou
ZIP/Postal Code
310003
Country
China
Facility Name
The First Hospital Affiliated of College Medicine, Zhejiang University
City
Hangzhou
ZIP/Postal Code
310009
Country
China
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
ZIP/Postal Code
200003
Country
China
Facility Name
Shanghai 6th People's Hospital
City
Shanghai
ZIP/Postal Code
200233
Country
China
Facility Name
Changhai Hospital
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
ZIP/Postal Code
215006
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
23782711
Citation
Hou J, Du X, Jin J, Cai Z, Chen F, Zhou DB, Yu L, Ke X, Li X, Wu D, Meng F, Ai H, Zhang J, Wortman-Vayn H, Chen N, Mei J, Wang J. A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. J Hematol Oncol. 2013 Jun 19;6:41. doi: 10.1186/1756-8722-6-41.
Results Reference
background
Links:
URL
http://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/clinical-study-report-csr-synopses/purposes-of-posting-clinical-study-report-csr-synopses
Description
Link to CSR synopsis
Learn more about this trial
Study of Lenalidomide and Low-Dose Dexamethasone in Chinese Subjects With Relapsed/Refractory Multiple Myeloma
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