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Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01615029
Recruitment Status : Active, not recruiting
First Posted : June 8, 2012
Results First Posted : April 14, 2017
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE June 6, 2012
First Posted Date  ICMJE June 8, 2012
Results First Submitted Date  ICMJE February 2, 2017
Results First Posted Date  ICMJE April 14, 2017
Last Update Posted Date November 8, 2019
Actual Study Start Date  ICMJE June 26, 2012
Actual Primary Completion Date October 2, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2017)
  • Phase 1: Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
    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) [ Time Frame: Up to 3 years ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2012)
Establish the safety profile of daratumumab when given in combination with Len/Dex [ Time Frame: Last patient Last treatment of Part 2 - maximum 24 cycles (approximately 2 years) or until progression. ]
Change History Complete list of historical versions of study NCT01615029 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2017)
  • Phase 2: Time to Progression (TTP) [ Time Frame: Up to 3 years ]
    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 [ Time Frame: Up to 3 years ]
    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) [ Time Frame: Up to 3 years ]
    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 Frame: Up to 3 years ]
    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 Frame: Up to 3 years ]
    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) [ Time Frame: Up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2012)
  • Evaluate the efficacy of daratumumab when given in combination with Len/Dex [ Time Frame: Last patient Last treatment of Part 2 - maximum 24 cycles (approximately 2 years) or until progression. ]
  • Evaluate the PK profile of daratumumab when given in combination with Len/Dex [ Time Frame: Last patient Last treatment of Part 2 - maximum 24 cycles (approximately 2 years) or until progression. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Part 1 (Dose Escalation): Daratumumab
    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.
  • Drug: Part 2 (Dose Expansion): Daratumumab
    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.
  • Drug: Lenalidomide
    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.
  • Drug: Dexamethasone
    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.
Study Arms  ICMJE Experimental: Daratumumab
Participants will receive daratumumab along with Lenalidomide and dexamethasone.
Interventions:
  • Drug: Part 1 (Dose Escalation): Daratumumab
  • Drug: Part 2 (Dose Expansion): Daratumumab
  • Drug: Lenalidomide
  • Drug: Dexamethasone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 9, 2015)
45
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2012)
50
Estimated Study Completion Date  ICMJE December 8, 2023
Actual Primary Completion Date October 2, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   France,   Netherlands,   United Kingdom,   United States
Removed Location Countries Italy
 
Administrative Information
NCT Number  ICMJE NCT01615029
Other Study ID Numbers  ICMJE CR101391
GEN503 ( Other Identifier: Genmab )
DARA-GEN503 ( Other Identifier: Janssen Research & Development, LLC )
2011-005709-62 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Principal Investigator: Torben Plesner, MD Vejle Hospital
Principal Investigator: Paul Richardson, MD Dana Farber
PRS Account Janssen Research & Development, LLC
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP