Study of Lenalidomide and Low-Dose Dexamethasone in Chinese Subjects With Relapsed/Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01593410
First received: May 4, 2012
Last updated: April 18, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Complete Response (CR) or partial Response (PR) using the European Group for Blood and Marrow Transplantation (EBMT) (Bladé) criteria.


Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
    Number of participants with Adverse Events

  • Progression Free Survival (PFS) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Number of participants who survive without progressing by the EBMT (Bladé) criteria

  • Overall Survival [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Number of participants alive

  • Response duration [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Length of time participants respond

  • Maximum observed concentration in plasma [ Time Frame: Days 1, 2, 7, 8, and 9 of Cycle 1 ] [ Designated as safety issue: No ]
    Pharmacokinetics - Cmax

  • Area under the plasma concentration-time curve [ Time Frame: Days 1, 2, 7, 8, and 9 of Cycle 1 ] [ Designated as safety issue: No ]
    Pharmacokinetics - AUC

  • Time to maximum concentration [ Time Frame: Days 1, 2, 7, 8, and 9 of Cycle 1 ] [ Designated as safety issue: No ]
    PK- Tmax

  • Terminal half-life [ Time Frame: Days 1, 2, 7, 8, and 9 of Cycle 1 ] [ Designated as safety issue: No ]
    Pharmacokinetics - T1/2

  • Apparent total body clearance [ Time Frame: Days 1, 2, 7, 8, and 9 of Cycle 1 ] [ Designated as safety issue: No ]
    Pharmacokinetics - CL/F

  • Apparent volume of distribution [ Time Frame: Days 1, 2, 7, 8, and 9 of Cycle 1 ] [ Designated as safety issue: No ]
    Pharmacokinetics - Vz/F


Enrollment: 194
Study Start Date: August 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Lenalidomide
25 mg oral lenalidomide once daily on Days 1-21 every 28 days
Other Name: Revlimid
Drug: Dexamethasone
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Understand and voluntarily sign informed consent form
  2. Age ≥ 18 years at the time of signing consent
  3. 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.
  4. 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).
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  6. Able to adhere to the study visit schedule and other protocol requirements.
  7. Must agree to comply to Lenalidomide Pregnancy Prevention Risk Management Plan requirements.

Exclusion Criteria

  1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Subjects with non-secretory multiple myeloma by Serum Protein Electrophoresis (SPEP) and Urine Protein Electrophoresis (UPEP) assessment.
  3. Pregnant or lactating females
  4. 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)
  5. 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.
  6. Significant active cardiac disease within the previous 6 months.
  7. 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
  8. Incidental histologic finding of prostate cancer (Tumor, Node, and Metastasis [TNM] stage of T1a or T1b)
  9. Known hypersensitivity to thalidomide or dexamethasone
  10. Prior history of uncontrollable side effects to dexamethasone therapy
  11. Peripheral neuropathy ≥ grade 2
  12. Prior use of lenalidomide
  13. 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)
  14. Unable or unwilling to undergo antithrombotic therapy
  15. History of deep vein thrombosis (DVT) or pulmonary emboli (PE) within the past 12 months
  16. Known HIV positivity
  17. 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593410

Locations
China
307 Hospital of Chinese PLA
Beijing, China, 100071
Chinese PLA General Hospital
Beijing, China, 300200
Peking Union Medical College Hospital
Beijing, China, 100730
Peking University Third Hospital
Beijing, China, 100081
Xiangya Hospital of Central- South University
Changsha, China, 410008
Nanfang Hospital of Southern Medical University
Guangzhou, China, 510515
Guangdong General Hospital
Guangzhou, China, 510080
The First Hospital Affiliated of College Medicine, Zhejiang University
Hangzhou, China, 310009
The First Hospital Affiliated of College Medicine, Zhejiang University
Hangzhou, China, 310003
Shanghai Changzheng Hospital
Shanghai, China, 200003
Shanghai 6th People's Hospital
Shanghai, China, 200233
Changhai Hospital
Shanghai, China, 200433
The First Affiliated Hospital of Soochow University
Suzhou, China, 215006
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Jay Mei, M.D. Celgene Corporation
  More Information

No publications provided by Celgene Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01593410     History of Changes
Other Study ID Numbers: CC-5013-MM-021
Study First Received: May 4, 2012
Last Updated: April 18, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Celgene Corporation:
Efficacy/Safety
Lenalidomide and Low-Dose Dexamethasone
Chinese Subjects
Relapsed/Refractory Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 22, 2014