Back to resultsDaratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Part 1 (Dose Escalation): Daratumumab
Part 2 (Dose Expansion): Daratumumab
Lenalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Daratumumab, Lenalidomide, Dexamethasone, Dose-escalation, Relapsed multiple myeloma, Relapsed and refractory multiple myeloma
Eligibility Criteria
Inclusion Criteria:
- (Part 1) Have relapsed multiple myeloma after receiving a minimum of 2 and a maximum of 4 prior lines of therapy and be eligible for treatment with lenalidomide and dexamethasone (Len/Dex)
- (Part 2) Have received at least 1 prior line of therapy for multiple myeloma
- Be older than or be 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status (0-2)
- Provide signed informed consent after receipt of oral and written information about the study and before any study-related activity is performed
Exclusion Criteria:
- Have previously received an allogenic stem cell transplant
- Have received autologous stem cell transplant within 12 weeks before the first infusion
- Have received antimyeloma treatment, radiotherapy, or any experimental drug or therapy within 2 weeks before the first infusion
- Have discontinued lenalidomide due to any treatment-related adverse event or be refractory to any dose of lenalidomide. Refractory to lenalidomide is defined as either, participants whose disease progresses within 60 days of lenalidomide, or participants whose disease is nonresponsive while on any dose of lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an minimal response (MR) or development of progressive disease (PD) while on lenalidomide
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Daratumumab
Arm Description
Participants will receive daratumumab along with Lenalidomide and dexamethasone.
Outcomes
Primary Outcome Measures
Phase 1: Percentage of Participants With Overall Response Rate (ORR)
ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). International Myeloma Working Group (IMWG) criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.
Phase 2: Percentage of Participants With Overall Response Rate (ORR)
ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). IMWG criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: greater than eqaul to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.
Secondary Outcome Measures
Phase 2: Time to Progression (TTP)
TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of >=25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL) Urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase must be >10 mg/dL; Bone marrow plasma cell percentage: the absolute % must be >=10 %; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method.
Phase 2: Duration of Response
Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.
Phase 2: Progression-Free Survival (PFS)
Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.
Phase 1: Time to Response
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment.
Phase 2: Time to Response
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment.
Phase 2: Overall Survival (OS)
Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan Meier method.
Full Information
NCT ID
NCT01615029
First Posted
June 6, 2012
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01615029
Brief Title
Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma
Official Title
An Open Label, International, Multicenter, Dose Escalating Phase I/II Trial Investigating the Safety of Daratumumab in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Relapsed and Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2012 (Actual)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to establish the safety profile of daratumumab when given in combination with Lenalidomide and dexamethasone in participants with relapsed or relapsed and refractory Multiple Myeloma (MM).
Detailed Description
The study is conducted in two parts. The dose escalation portion of the trial (Part 1) participants are enrolled into cohorts at increasing dose levels of daratumumab in combination with Len/Dex in 28 day treatment cycles. Part 2, the cohort expansion part of the trial, will further explore the maximum tolerated dose (MTD) (or the maximum tested dose) of daratumumab as determined in Part 1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Daratumumab, Lenalidomide, Dexamethasone, Dose-escalation, Relapsed multiple myeloma, Relapsed and refractory multiple myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Daratumumab
Arm Type
Experimental
Arm Description
Participants will receive daratumumab along with Lenalidomide and dexamethasone.
Intervention Type
Drug
Intervention Name(s)
Part 1 (Dose Escalation): Daratumumab
Intervention Description
Participants will receive intravenous (injection of a substance into a vein) infusion of daratumumab in an increased fashion from 2 milligram per kilogram (mg/kg) up to maximum dose of 16 mg/kg. Considering the safety and efficacy of dose in Part 1, recommended phase 2 dose (RP2D) for Part 2 of the study will be decided. A predose infusion of 10 percent (%) of the full dose of daratumumab will be administered a day before the first full infusion of the first cycle. Participants will receive 4 weekly infusions in the first 2 treatment cycles. From cycles 3 to 6 infusions will be administered every alternate week and monthly infusions will be administered from cycle 7 until disease progression.
Intervention Type
Drug
Intervention Name(s)
Part 2 (Dose Expansion): Daratumumab
Intervention Description
Participants will receive RP2D as determined in Part 1 of the study. Participants will receive 4 weekly infusions of RP2D in the first 2 treatment cycles. From cycles 3 to 6 infusions will be administered every alternate week and monthly infusions will be administered from cycle 7 until disease progression.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
All participants (Part 1 and Part 2) will receive 25 mg lenalidomide orally (by mouth) from days 1 to 21 of each 28-day cycle until disease progression.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
All participants (Part 1 and Part 2) will receive 40 mg (20 mg intravenously [injection of a substance into a vein]) dexamethasone once weekly. Participants older than 75 years or underweight (body mass index [BMI] less than [<] 18.5), the dexamethasone dose will be administered at a dose of 20 mg once weekly until disease progression.
Primary Outcome Measure Information:
Title
Phase 1: Percentage of Participants With Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). International Myeloma Working Group (IMWG) criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.
Time Frame
Up to 3 years
Title
Phase 2: Percentage of Participants With Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). IMWG criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: greater than eqaul to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Phase 2: Time to Progression (TTP)
Description
TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of >=25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL) Urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase must be >10 mg/dL; Bone marrow plasma cell percentage: the absolute % must be >=10 %; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method.
Time Frame
Up to 3 years
Title
Phase 2: Duration of Response
Description
Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.
Time Frame
Up to 3 years
Title
Phase 2: Progression-Free Survival (PFS)
Description
Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.
Time Frame
Up to 3 years
Title
Phase 1: Time to Response
Description
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment.
Time Frame
Up to 3 years
Title
Phase 2: Time to Response
Description
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment.
Time Frame
Up to 3 years
Title
Phase 2: Overall Survival (OS)
Description
Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan Meier method.
Time Frame
Up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
(Part 1) Have relapsed multiple myeloma after receiving a minimum of 2 and a maximum of 4 prior lines of therapy and be eligible for treatment with lenalidomide and dexamethasone (Len/Dex)
(Part 2) Have received at least 1 prior line of therapy for multiple myeloma
Be older than or be 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status (0-2)
Provide signed informed consent after receipt of oral and written information about the study and before any study-related activity is performed
Exclusion Criteria:
Have previously received an allogenic stem cell transplant
Have received autologous stem cell transplant within 12 weeks before the first infusion
Have received antimyeloma treatment, radiotherapy, or any experimental drug or therapy within 2 weeks before the first infusion
Have discontinued lenalidomide due to any treatment-related adverse event or be refractory to any dose of lenalidomide. Refractory to lenalidomide is defined as either, participants whose disease progresses within 60 days of lenalidomide, or participants whose disease is nonresponsive while on any dose of lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an minimal response (MR) or development of progressive disease (PD) while on lenalidomide
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Torben Plesner, MD
Organizational Affiliation
Vejle Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Richardson, MD
Organizational Affiliation
Dana Farber
Official's Role
Principal Investigator
Facility Information:
City
Boston
State/Province
Massachusetts
Country
United States
City
Copenhagen Ø
Country
Denmark
City
Vejle
Country
Denmark
City
Lille Cedex
Country
France
City
Nantes N/a
Country
France
City
Vandoeuvre les Nancy
Country
France
City
Utrecht
Country
Netherlands
City
London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29025767
Citation
Krejcik J, Frerichs KA, Nijhof IS, van Kessel B, van Velzen JF, Bloem AC, Broekmans MEC, Zweegman S, van Meerloo J, Musters RJP, Poddighe PJ, Groen RWJ, Chiu C, Plesner T, Lokhorst HM, Sasser AK, Mutis T, van de Donk NWCJ. Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab. Clin Cancer Res. 2017 Dec 15;23(24):7498-7511. doi: 10.1158/1078-0432.CCR-17-2027. Epub 2017 Oct 12.
Results Reference
derived
PubMed Identifier
27531679
Citation
Plesner T, Arkenau HT, Gimsing P, Krejcik J, Lemech C, Minnema MC, Lassen U, Laubach JP, Palumbo A, Lisby S, Basse L, Wang J, Sasser AK, Guckert ME, de Boer C, Khokhar NZ, Yeh H, Clemens PL, Ahmadi T, Lokhorst HM, Richardson PG. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood. 2016 Oct 6;128(14):1821-1828. doi: 10.1182/blood-2016-07-726729. Epub 2016 Aug 16.
Results Reference
derived
Learn more about this trial
Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma
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