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A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02951819
Recruitment Status : Active, not recruiting
First Posted : November 1, 2016
Results First Posted : April 3, 2019
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Scientific Affairs, LLC

Tracking Information
First Submitted Date  ICMJE October 31, 2016
First Posted Date  ICMJE November 1, 2016
Results First Submitted Date  ICMJE March 8, 2019
Results First Posted Date  ICMJE April 3, 2019
Last Update Posted Date September 11, 2020
Actual Study Start Date  ICMJE November 9, 2016
Actual Primary Completion Date March 8, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2019)
Percentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR) [ Time Frame: After 4 cycles of Induction (Approximately 4 months) ]
Percentage of participants who achieved CR or VGPR (as per International Myeloma Working Group [IMWG] criteria) was reported. CR: negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percent (%) plasma cells (PC) in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90% reduction in serum M-protein plus urine M-protein level < 100 milligram per 24 hours (mg/24hours).
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2016)
Complete Response plus Very Good Partial (CR+VGPR) Response Rate [ Time Frame: Approximately 4 Months ]
Percentage of subjects achieving complete response plus very good partial response rate (CR+VGPR) according to International Myeloma Working Group (IMWG) criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2019)
  • Overall Response Rate (ORR) [ Time Frame: After 4 Cycles of Induction (4 months), at End of Induction (4 to 8 months) and at the End of Maintenance (12 months) ]
    ORR: percentage of participants achieved PR or better (PR,VGPR,CR,sCR) per IMWG. CR:negative immunofixation on serum, urine, disappearance of soft tissue plasmacytomas,<5% PCs in bone marrow(BM). sCR:CR plus normal FLC ratio,absence of clonal cells in BM by immunohistochemistry, immunofluorescence. VGPR:Serum, urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24hours. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200mg/24hours. If serum, urine M-protein unmeasurable, a>=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum, urine M-protein not measurable, serum free light assay is not measurable,>=50% reduction in PCs required in place of M-protein,provided baseline bone marrow PCs% >=30%, if present at baseline, a >=50% reduction in size of soft tissue plasmacytomas is also required.
  • Time to Very Good Partial Response (VGPR) or Better [ Time Frame: Approximately 12 months ]
    Time to VGPR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (VGPR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. VGPR is defined by IMWG criteria as serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 % reduction in serum M-protein plus urine M-protein level < 100 milligram/24 hours (mg/24 hours).
  • Time to Partial Response (PR) or Better [ Time Frame: Approximately 12 months ]
    Time to PR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (PR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. PR is defined as per IMWG criteria as >= 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >= 90% or to < 200 mg/24hours. If the serum and urine M-protein are unmeasurable, a>= 50% decrease in the difference between involved and uninvolved Free light chain (FLC) levels is required in the place of the M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cells percentage was >=30%. In addition to the above listed criteria, if present at baseline, a >= 50% reduction in the size of soft tissue plasmacytomas is also required.
  • Duration of Response (DOR) [ Time Frame: Approximately 15 months ]
    DOR was defined for participants with a confirmed response (PR or better) as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria or death due to progressive disease. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200 mg/24hours. If serum and urine M-protein are unmeasurable, a >=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in PCs is required in place of M-protein, provided baseline bone marrow PCs % was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
  • Progression Free Survival (PFS) [ Time Frame: Approximately 15 months ]
    PFS: duration from date of first dose (start of induction) to date of first documented evidence of progressive disease (PD) based on computerized algorithm per IMWG criteria or death due to any cause, whichever occurred first. PD: 25% increase from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/dL and >=200 mg/24 hours respectively);Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL);Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
  • Time to Disease Progression (TTP) [ Time Frame: Approximately 15 months ]
    TTP was defined as the time between the date of first dose (start of induction) and the date of first documented evidence of confirmed PD, as defined in the IMWG response criteria. PD per IMWG criteria: Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/deciliter (dL) and >=200 mg/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.
  • Overall Survival (OS) [ Time Frame: Approximately 15 months ]
    Overall survival (OS) was measured from the date of first dose (start of induction) to the date of death due to any cause.
  • Percentage of Participants With Treatment Emergent-Adverse Event [ Time Frame: Approximately 15 months ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and approximately up to 15 months that were absent before treatment or that worsened relative to pre-treatment state.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2016)
  • Overall Response Rate (ORR) [ Time Frame: Following 4 cycles (each cycle is of 28 days), end of induction (4-8 cycles), at start of maintenance therapy and after end of maintenance therapy (12 months) ]
    Percentage of subjects who achieve complete response (CR), very good partial response (VGPR) or partial response (PR) according to IMWG criteria.
  • Time to Very Good Partial Response (VGPR) or Better [ Time Frame: Up to End of Treatment (Approximately 36 months) ]
    Time to VGPR or better is defined as the duration from the date of start of induction therapy to the date of initial documentation of VGPR or better, which is confirmed by a repeated measurement as required by the IMWG criteria.
  • Time to Partial Response or Better [ Time Frame: Up to End of Treatment (Approximately 36 months) ]
    Time to partial response is defined as the duration from the date of start of induction therapy to the date of initial documentation of PR or better, which is confirmed by a repeated measurement as required by the IMWG criteria.
  • Duration of Response (DoR) [ Time Frame: Up to End of Treatment (Approximately 36 months) ]
    Duration of response is defined as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria.
  • Progression Free Survival (PFS) Rate [ Time Frame: 36 Months (approximately at 1 year and 3 years) ]
    Percentage of subjects who have not developed progressive disease and are at alive at 1 year and 3 years after study entry.
  • Overall Survival Rate [ Time Frame: 36 Months (approximately at 1 year and 3 years) ]
    Percentage of subjects who are alive at 1 year and 3 years after study entry.
  • Number of Subjects with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to End of Treatment (Approximately 36 months) ]
  • Infusion Reaction Profile of Split-Dose Infusions of Daratumumab [ Time Frame: Day 1 and Day 2 of Cycle 1 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma
Official Title  ICMJE Daratumumab Plus Cyclophosphamide, Bortezomib and Dexamethasone (Dara-CyBorD) in Previously Untreated and Relapsed Subjects With Multiple Myeloma
Brief Summary The purpose of this study is to evaluate complete response plus (+) very good partial response (CR+VGPR) rate following 4 cycles of induction therapy of daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD), in previously untreated subjects, and in relapsed subjects with multiple myeloma, as defined by the International Myeloma Working Group (IMWG) criteria.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Daratumumab

    For induction therapy cycle 1 day 1 and day 2 doses of daratumumab will be 8 milligram/kilogram (mg/kg). Starting cycle 1 week 2 until the completion of week 8 of daratumumab patients will receive 16 mg/kg Intravenously (IV) weekly.

    Starting week 9 until the completion of week 24 therapy daratumumab will be administered every other week at 16 mg/kg IV.

    Starting week 25 and beyond for induction therapy daratumumab will be given once every 4 weeks.

  • Drug: Cyclophosphamide
    Subjects will receive 4 to 8 cycles of oral cyclophosphamide 300 milligram per meter square (mg/m^2 ) on Days 1, 8, 15, and 22 for every 28 days.
  • Drug: Bortezomib
    Subjects will receive 4 to 8 cycles of Bortezomib 1.5 mg/m2 subcutaneous (SC) on Days 1, 8, and 15 for every 28 days.
  • Drug: Dexamethasone
    Subjects will be given corticosteroids (Dexamethasone) as pre-infusion therapy prior to daratumumab and for the first 8 cycles will also receive post-infusion corticosteroids (Dexamethasone).
Study Arms  ICMJE Experimental: Dara-CyBorD
Subjects will receive Daratumumab along with Cyclophosphamide, Bortezomib and Dexamethasone (Dara-CyBorD) as induction on a 28-day cycle length and Daratumab and Dexamethasone on Day 1 of each cycle for 12 cycles as maintenance therapy.
Interventions:
  • Drug: Daratumumab
  • Drug: Cyclophosphamide
  • Drug: Bortezomib
  • Drug: Dexamethasone
Publications * Not Provided

*   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: March 9, 2018)
101
Original Estimated Enrollment  ICMJE
 (submitted: October 31, 2016)
100
Estimated Study Completion Date  ICMJE September 30, 2020
Actual Primary Completion Date March 8, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with documented multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) 2015 criteria: Clonal bone marrow plasma cells greater than or equal to (>=) 10 percent (%) or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB (calcium level, renal dysfunction, anemia, and destructive bone lesions) features and myeloma defining events as in the protocol
  • Subjects with previously untreated myeloma or relapsed myeloma with one prior line of therapy including an induction regimen which may be followed by autologous stem cell transplantation and single agent maintenance therapy. For previously untreated subjects an emergency course of steroids (defined as no greater than 40 milligram (mg) of dexamethasone, or equivalent per day for a maximum of 4 days) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • A woman of childbearing potential must have 2 negative serum (beta (β) human chorionic gonadotropin) or urine pregnancy tests during screening, the first one within 28 days prior to the first dose of study drug and the second within 24 hours prior to the first dose of study drug
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control example, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:

  • Refractory to any proteasome inhibitor (PI) or the combination of PI and immunomodulatory drug (IMiD) agents (such as lenalidomide), defined as failure to respond or progression within 60 days of the end of PI therapy
  • Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma
  • Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
  • Has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
  • Is known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02951819
Other Study ID Numbers  ICMJE CR108235
54767414MMY2012 ( Other Identifier: Janssen Scientific Affairs, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Scientific Affairs, LLC
Study Sponsor  ICMJE Janssen Scientific Affairs, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Scientific Affairs, LLC Clinical Trial Janssen Scientific Affairs, LLC
PRS Account Janssen Scientific Affairs, LLC
Verification Date September 2020

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