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A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory 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: NCT03277105
Recruitment Status : Active, not recruiting
First Posted : September 8, 2017
Last Update Posted : March 6, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE September 7, 2017
First Posted Date  ICMJE September 8, 2017
Last Update Posted Date March 6, 2020
Actual Study Start Date  ICMJE October 27, 2017
Actual Primary Completion Date June 27, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 20, 2020)
  • Overall Response Rate (ORR) [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) ]
    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 mg/24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in 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 bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage 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.
  • Maximum Trough Concentration (Ctrough) of Daratumumab [ Time Frame: Cycle 3 (each cycle 28 days) Day 1 ]
    Maximum Ctrough is defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Original Primary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • Overall Response Rate (ORR) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) ]
    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to lesss than (<) 200 mg/24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the Mprotein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage 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.
  • Maximum Trough Concentration (Ctrough) of Daratumumab [ Time Frame: Cycle 3 (each cycle 28 days) Day 1 ]
    Maximum Ctrough is defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2020)
  • Percentage of participants With Infusion-Related Reactions (IRR) [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) ]
    The Percentage of Participants with infusion reactions will be reported.
  • Progression-Free Survival (PFS) [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    PFS is defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. IMWG criteria: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
  • Very Good Partial Response (VGPR) or Better Rate [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]), IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cellS (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
  • Complete Response (Including sCR) or Better Rate [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    As per IMWG criteria for CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.
  • Time to Next Treatment [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    Time to next therapy is defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
  • Overall Survival (OS) [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    OS is defined as the time from the date of randomization to the date of the participant's death.
  • Patient-Reported Satisfaction With Therapy [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    Patient-reported satisfaction with therapy is defined as the mean of responses to 7 of 9 questions in the modified cancer therapy satisfaction questionnaire (modified-CTSQ). Modified-CTSQ contain 9 items specific to satisfaction with therapy and for comparison of IV with SC administration. Satisfaction with therapy is calculated based on 7-items using 5-point verbal rating scale, 1, never; 5, always. Scores will be averaged and transformed to a 0-100 scale; higher scores represent better health.
  • Duration of Response [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    Duration of response is as from initial date of first response to date of disease progression or death.
  • Time to response [ Time Frame: At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years) ]
    Time to response is defined as the time from randomization until onset of first response.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • Percentage of participants With Infusion-Related Reactions (IRR) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) ]
    The Percentage of Participants with infusion reactions will be reported.
  • Progression-Free Survival (PFS) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    PFS is defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. According to IMWG criteria: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
  • Very Good Partial Response (VGPR) or Better Rate [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cellS (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
  • Complete Response (Including sCR) or Better Rate [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Complete response is based on serum M-Protein assessments. IMWG criteria for CR: Negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.
  • Time to Next Treatment [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Time to next therapy is defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
  • Overall Survival (OS) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    OS is defined as the time from the date of randomization to the date of the participant's death.
  • Patient-Reported Satisfaction With Therapy [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Patient-reported satisfaction with therapy is defined as the mean of responses to 7 of 9 questions in the modified cancer therapy satisfaction questionnaire (modified-CTSQ). Modified-CTSQ contain 9 items specific to satisfaction with therapy and for comparison of IV with SC administration. Satisfaction with therapy is calculated based on 7-items using 5-point verbal rating scale, 1, never; 5, always. Scores will be averaged and transformed to a 0-100 scale; higher scores represent better health.
  • Duration of Response [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Duration of response is defined as date of onset of first response until date of disease progression or death.
  • Time to response [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Time to response is defined as the time from randomization until onset of first response.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
Brief Summary The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).
Detailed Description The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Dara SC
    Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 U/mL, once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
  • Drug: Dara IV
    Participants will receive Dara IV 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
    Other Name: JNJ-54767414
Study Arms  ICMJE
  • Experimental: Dara SC
    Participants will receive a fixed dose of daratumumab as 1800 milligram (mg) subcutaneously (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.
    Intervention: Drug: Dara SC
  • Active Comparator: Dara IV
    Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.
    Intervention: Drug: Dara IV
Publications * Mateos MV, Nahi H, Legiec W, Grosicki S, Vorobyev V, Spicka I, Hungria V, Korenkova S, Bahlis N, Flogegard M, Bladé J, Moreau P, Kaiser M, Iida S, Laubach J, Magen H, Cavo M, Hulin C, White D, De Stefano V, Clemens PL, Masterson T, Lantz K, O'Rourke L, Heuck C, Qin X, Parasrampuria DA, Yuan Z, Xu S, Qi M, Usmani SZ. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020 Mar 23. pii: S2352-3026(20)30070-3. doi: 10.1016/S2352-3026(20)30070-3. [Epub ahead of print]

*   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: May 28, 2019)
522
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2017)
480
Estimated Study Completion Date  ICMJE December 26, 2023
Actual Primary Completion Date June 27, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen
  • Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy
  • Documented multiple myeloma as defined by the criteria below:

    1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
    2. Measurable disease at Screening as defined by any of the following:

      1. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
      2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Meet the clinical laboratory criteria as specified in the protocol
  • Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Exclusion Criteria:

  • Received daratumumab or other anti-CD38 therapies previously
  • Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days before treatment
  • Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing)
  • Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)
  • History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
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 Australia,   Brazil,   Canada,   Czechia,   France,   Greece,   Israel,   Italy,   Japan,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Sweden,   Taiwan,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03277105
Other Study ID Numbers  ICMJE CR108342
2017-000206-38 ( EudraCT Number )
54767414MMY3012 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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
PRS Account Janssen Research & Development, LLC
Verification Date March 2020

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