A Phase 2 Study of Lenalidomide to Evaluate the Efficacy in Japanese Patients With Newly Diagnosed Multiple Myeloma

A Phase 2, Multicenter, Open-label, Single Arm Study of Lenalidomide (CC-5013) in Combination With Low-dose Dexamethasone in Japanese Patients With Previously Untreated Multiple Myeloma

To determine the efficacy of lenalidomide in combination with low-dose dexamethasone in Japanese subjects with previously untreated multiple myeloma.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kagoshima, Japan, 892-0853
    • Kagoshima Medical Center
  • Kyoto, Japan, 602-8566
    • University Hospital, Kyoto Prefectural University of Medicine
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 701-1192
    • Okayama Medical Center
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
  • Tokyo, Japan, 150-8935
    • Japanese Red Cross Medical Center
  • Aichi
    • Nagoya, Aichi, Japan, 466-8650
      • Nagoya Daini Red Cross Hospital
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
  • Chiba
    • Kamogawa, Chiba, Japan, 296-8602
      • Kameda Medical Center
    • Narita, Chiba, Japan, 286-8523
      • Japanese Red Cross Narita Hospital
  • Ehime
    • Touon, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Gunma
    • Shibukawa, Gunma, Japan, 377-8511
      • Nishigunma National Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Ibaraki
    • Hitachi, Ibaraki, Japan, 317-0077
      • Hitachi General Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8602
      • Kurashiki Central Hospital
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kinki University Hospital, Faculty of Medicine
  • Shizuoka
    • Sunto, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Tachikawa, Tokyo, Japan, 190-0014
      • National Disaster Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 20 years at the time of signing the informed consent document
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted
• Able to adhere to the study visit schedule and other protocol requirements
• Previously untreated, symptomatic multiple myeloma
• Have measurable disease by protein electrophoresis analyses
• At least 65 years of age or older or, if younger than 65 years of age, not candidates for hematopoietic stem cell transplantation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Must agree to comply to Lenalidomide Pregnancy Prevention Risk Management Plan

Exclusion Criteria:

• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Any condition that confounds the ability to interpret data from the study
• Previous treatment with anti-myeloma therapy
• Pregnant or lactating females

• Any of the following laboratory abnormalities:

  • Absolute neutrophil count (ANC) < 1,000/microL (1.0 × 10^9/L )
  • Untransfused platelet count (a platelet count drawn at least 7 days after the administration of the last platelet transfusion) < 50,000 cells/microL (50 × 10^9/L)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 × upper limit of normal
• Renal failure requiring hemodialysis or peritoneal dialysis
• Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years
• Subjects who are unable or unwilling to undergo antithrombotic therapy.
• Peripheral neuropathy of ≥ grade 2 severity.
• Uncontrolled systemic fungal, bacterial, or viral infection
• Known human immunodeficiency virus (HIV) positivity (subjects who are receiving antiretroviral therapy for HIV disease)
• Hepatitis Bs (HBs) antigen-positive, or hepatitis C virus (HCV) antibody-positive. In case HBc antibody and/or HBs antibody is positive even if HBs antigen-negative, a Hepatitis B virus (HBV) DNA test should be performed and if positive the subject will be excluded.
• Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.
• Ineligible for dexamethasone or dexamethasone is contraindicated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide plus dexamethasone; Lenalidomide plus low-dose dexamethasone	Drug: Lenalidomide; 25 mg oral lenalidomide once daily on Days 1-21 of each 28-day cycle; Other Names: Revlimid; Drug: dexamethasone; 40 mg oral dexamethasone once daily on Days 1, 8, 15 and 22 of each 28-day cycle; Other Names: LenaDex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Number of Complete Responses (CR) plus Very Good Partial Response (VGPR) plus Partial Response (PR) based on the International Myeloma Working Group criteria (IMWG). Any participant who achieved a CR, VGPR, or PR while on study treatment was defined as a responder. CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.	From first dose until the data cut-off date of 15 July 2014. Median time on follow-up was 61.6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Response	Time to response was calculated for the responders as the time from the first dose date to the initial documented response (CR, VGPR or PR). CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.	From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up time was 61.6 weeks.
Duration of Response	Duration of response was calculated for the responders as the time from the initial documented response (CR or VGPR or PR) to the first documented progression or death due to any cause, whichever occurred first. Duration of response for participants last known to be alive with no progression after a CR, VGPR, or PR were censored at the date of last adequate response assessment.	From the first dose of study drug treatment until the data cut-off date of 15 July2014. Median follow up time was 61.6 weeks.
Progression Free Survival (PFS)	PFS was calculated as the time from the first dose date to the first documented progression based on IWG criteria or death due to any cause, whichever occurred first. If progression or death was not documented at the time of data cutoff date, these observations were censored at the last adequate assessment date showing evidence of no progression or death.	From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow-up for PFS assessments was 61.6 weeks.
Overall Survival (OS)	The time from the start of study treatment to death due to any cause. OS was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.	From the first dose of study drug treatment until the data cut-off date of 15 July 2014. Median follow up is 14.2 months
Number of Participants With Adverse Events	An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.	From first dose of study drug treatment through to 28 days after the last dose, until the data cut-off date of 15 July 2014; median treatment duration was 60 weeks

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Toru Sasaki, Celgene K.K.

Publications and helpful links

General Publications

• Suzuki K, Shinagawa A, Uchida T, Taniwaki M, Hirata H, Ishizawa K, Matsue K, Ogawa Y, Shimizu T, Otsuka M, Matsumoto M, Iida S, Terui Y, Matsumura I, Ikeda T, Takezako N, Ogaki Y, Midorikawa S, Houck V, Ervin-Haynes A, Chou T. Lenalidomide and low-dose dexamethasone in Japanese patients with newly diagnosed multiple myeloma: A phase II study. Cancer Sci. 2016 May;107(5):653-8. doi: 10.1111/cas.12916. Epub 2016 Mar 30.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): November 26, 2013
• Study Completion (Actual): June 26, 2018

Study Registration Dates

• First Submitted: October 1, 2012
• First Submitted That Met QC Criteria: October 2, 2012
• First Posted (Estimate): October 3, 2012

Study Record Updates

• Last Update Posted (Actual): November 8, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Lenalidomide; dexamethasone; newly diagnosed multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide
• Other Study ID Numbers: CC-5013-MM-025