A Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone in Japanese Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Daratumumab (16 mg/kg)
Lenalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Participants with documented multiple myeloma (MM) satisfying the CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities) criteria , monoclonal plasma cells in the bone marrow more than equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable disease Measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G MM: serum monoclonal paraprotein (M protein) level >=1.0 gram/deciliter (dL) or urine M protein level >= 200 milligram(mg)/24 hours; or (b) IgA, IgM, IgD, or IgE MM: serum M protein level >=0.5 g/dL or urine M protein level >=200 mg/24 hours; or (c) Light chain MM without measurable disease in serum or urine: serum Ig free light chain (FLC) >=10 mg/dL and abnormal serum Ig kappa lambda FLC ratio
- Participants newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to being >=65 years old, or in subjects less than (<) 65 years old presence of important comorbid condition(s) likely to have a negative effect on the tolerability of high-dose chemotherapy with ASCT
- Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 4 weeks prior to dosing and the second within 3 days prior to dosing
Exclusion Criteria:
- Participants with diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering MM
- Participant with plasma cell leukemia or other conditions in which Ig (immunoglobulin) M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
- Participants who have prior or current systemic therapy or ASCT for MM, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment
- Participants with history of malignancy (other than MM) within 5 years before the date of the first daratumumab administration
- Participants who have radiation therapy within 14 days of the first dose
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Daratumumab with Lenalidomide and dexamethasone
Arm Description
Daratumumab (16 milligram per kilogram [mg/kg]) will be administered by intravenous [IV] infusion to all participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity or study end. Participants will receive lenalidomide 25 mg orally on Days 1 through 21 of each 28 day cycle. Participants will receive dexamethasone 40mg weekly, at day 1, 8, 15, 22 of each cycle.
Outcomes
Primary Outcome Measures
Dose limiting toxicity (DLT) to analyze the safety of daratumumab when combined with lenalidomide and dexamethasone
Number of Participants With Dose Limiting Toxicity During Cycle 1.
Secondary Outcome Measures
Rate of Complete Response (CR) or Better
CR is Defined as the proportion of Participants achieving CR (including stringent complete response [sCR]) according to the International Myeloma Working Group (IMWG) criteria.
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieve CR, Partial Response (PR), VGPR, and sCR according to the IMWG criteria, during or after study treatment.
Very good partial response (VGPR) or better (VGPR, CR, or sCR)
VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 pecent (%) reduction in serum M-protein plus urine M-protein level less than (<) 100 milligram(mg)/24 hour (h).
Minimum Observed Serum Concentration (Cmin)
The Cmin is the minimum observed analyte concentration.
Maximum Observed Concentration (Cmax)
The Cmax is the maximum observed analyte concentration.
Immunogenicity of daratumumab
Anti-daratumumab antibodies will be evaluated in serum samples collected for all the participants.
Full Information
NCT ID
NCT02918331
First Posted
September 27, 2016
Last Updated
April 2, 2020
Sponsor
Janssen Pharmaceutical K.K.
1. Study Identification
Unique Protocol Identification Number
NCT02918331
Brief Title
A Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone in Japanese Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation
Official Title
A Phase 1b Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone (DRd) in Japanese Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
October 2017 (Actual)
Study Completion Date
March 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Pharmaceutical K.K.
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety of daratumumab when combined with lenalidomide and dexamethasone in Japanese participants with newly diagnosed multiple myeloma who are not candidates for high-dose chemotherapy and autologous stem cell transplantation (ASCT).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Daratumumab with Lenalidomide and dexamethasone
Arm Type
Experimental
Arm Description
Daratumumab (16 milligram per kilogram [mg/kg]) will be administered by intravenous [IV] infusion to all participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity or study end.
Participants will receive lenalidomide 25 mg orally on Days 1 through 21 of each 28 day cycle.
Participants will receive dexamethasone 40mg weekly, at day 1, 8, 15, 22 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Daratumumab (16 mg/kg)
Intervention Description
Daratumumab (16 mg/kg) will be administered by IV infusion to all participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity or study end.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Participants will receive lenalidomide 25 mg orally on Days 1 through 21 of each 28 day cycle. Participants with creatinine clearance (CrCl) between 30 and 60 milliLitre (mL)/minute (min) will receive lenalidomide 10 mg every 24 hours.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Participants will receive dexamethasone 40 mg weekly, at day 1, 8, 15, 22 of each cycle.
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT) to analyze the safety of daratumumab when combined with lenalidomide and dexamethasone
Description
Number of Participants With Dose Limiting Toxicity During Cycle 1.
Time Frame
Cycle 1, Day 1 to Day 28
Secondary Outcome Measure Information:
Title
Rate of Complete Response (CR) or Better
Description
CR is Defined as the proportion of Participants achieving CR (including stringent complete response [sCR]) according to the International Myeloma Working Group (IMWG) criteria.
Time Frame
Approximately 3.7 years
Title
Overall Response Rate (ORR)
Description
ORR is defined as the percentage of participants who achieve CR, Partial Response (PR), VGPR, and sCR according to the IMWG criteria, during or after study treatment.
Time Frame
Approximately 3.7 years
Title
Very good partial response (VGPR) or better (VGPR, CR, or sCR)
Description
VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 pecent (%) reduction in serum M-protein plus urine M-protein level less than (<) 100 milligram(mg)/24 hour (h).
Time Frame
Approximately 3.7 years
Title
Minimum Observed Serum Concentration (Cmin)
Description
The Cmin is the minimum observed analyte concentration.
Time Frame
Cycle 1, Cycle 3, Cycle 6, Cycle 12 (each cycle of 28 days), End of Treatment (within 30 days of the last dose), and Follow-Up (8 weeks after the last dose)
Title
Maximum Observed Concentration (Cmax)
Description
The Cmax is the maximum observed analyte concentration.
Time Frame
Cycle 1, Cycle 3, Cycle 6, Cycle 12 (each cycle of 28 days), End of Treatment (within 30 days of the last dose), and Follow-Up (8 weeks after the last dose)
Title
Immunogenicity of daratumumab
Description
Anti-daratumumab antibodies will be evaluated in serum samples collected for all the participants.
Time Frame
Cycle 1, Cycle 3, Cycle 12 (each cycle of 28 days), End of Treatment (within 30 days of the last dose), and Follow-Up (8 weeks after the last dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants with documented multiple myeloma (MM) satisfying the CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities) criteria , monoclonal plasma cells in the bone marrow more than equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable disease Measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G MM: serum monoclonal paraprotein (M protein) level >=1.0 gram/deciliter (dL) or urine M protein level >= 200 milligram(mg)/24 hours; or (b) IgA, IgM, IgD, or IgE MM: serum M protein level >=0.5 g/dL or urine M protein level >=200 mg/24 hours; or (c) Light chain MM without measurable disease in serum or urine: serum Ig free light chain (FLC) >=10 mg/dL and abnormal serum Ig kappa lambda FLC ratio
Participants newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to being >=65 years old, or in subjects less than (<) 65 years old presence of important comorbid condition(s) likely to have a negative effect on the tolerability of high-dose chemotherapy with ASCT
Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase
Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 4 weeks prior to dosing and the second within 3 days prior to dosing
Exclusion Criteria:
Participants with diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering MM
Participant with plasma cell leukemia or other conditions in which Ig (immunoglobulin) M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
Participants who have prior or current systemic therapy or ASCT for MM, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment
Participants with history of malignancy (other than MM) within 5 years before the date of the first daratumumab administration
Participants who have radiation therapy within 14 days of the first dose
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Pharmaceutical K.K., Japan Clinical Trial
Organizational Affiliation
Janssen Pharmaceutical K.K.
Official's Role
Study Director
Facility Information:
City
Hiroshima
Country
Japan
City
Kanazawa
Country
Japan
City
Nagoya
Country
Japan
City
Osaka
Country
Japan
City
Shibuya
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
32002821
Citation
Takamatsu H, Iida S, Shibayama H, Shibayama K, Yamazaki H, Suzuki K. Daratumumab, lenalidomide, and dexamethasone in Japanese patients with transplant-ineligible newly diagnosed multiple myeloma: a phase 1b study. Int J Hematol. 2020 May;111(5):692-701. doi: 10.1007/s12185-020-02825-w. Epub 2020 Jan 30.
Results Reference
derived
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A Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone in Japanese Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation
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