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Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab Intravenous (Dara-IV)

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ClinicalTrials.gov Identifier: NCT03871829
Recruitment Status : Recruiting
First Posted : March 12, 2019
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE March 11, 2019
First Posted Date  ICMJE March 12, 2019
Last Update Posted Date January 31, 2020
Actual Study Start Date  ICMJE May 31, 2019
Estimated Primary Completion Date September 14, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response [ Time Frame: Approximately 2 years ]
Percentage of participants achieving VGPR or better response according IMWG criteria for VGPR will be reported. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03871829 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2019)
  • Overall Response Rate (ORR) [ Time Frame: Approximately 2 years ]
    ORR is defined as percentage of participants who achieve partial response (PR) or better (including VGPR, CR, sCR) responses prior to subsequent anti-myeloma therapy. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <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%; additionally, if present at baseline, a >=50% reduction in the size of soft tissue PCs is also required.
  • Percentage of Participants Achieving Complete Response (CR) or Stringent Complete Response (sCR) [ Time Frame: Approximately 2 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 (PCs), and <5% PCs in bone marrow. IMWG criteria for sCR defined as, CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescencea or 2- to 4- color flow cytometry.
  • Progression Free Survival (PFS) [ Time Frame: Up to approximately 3.3 years ]
    PFS is time from date of randomization to date of documented progressive disease (PD) on first line treatment given for multiple myeloma (MM) or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.
  • Overall Survival (OS) [ Time Frame: Up to approximately 3.3 years ]
    OS is defined as the time from the date of first dose of study drug to date of death due to any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
  • Percentage of Participants With Negative Minimal Residual Disease (MRD) [ Time Frame: Approximately 2 years ]
    Percentage of participants who have achieved MRD negative status will be assessed.
  • Time to Next Treatment [ Time Frame: Up to approximately 3.3 years ]
    Time to next treatment is defined as the time from randomization to the start of the next-line treatment.
  • Serum Concentrations of Daratumumab [ Time Frame: Arm A: Cycle 1 (each cycle of 28 days) Day 1 (Cycle 1 Day 1), Cycle 3 Day 1; Arm B: Cycle 1 Day1, Cycle 3 Day 1, Cycle 7 Day 1 and Follow Up (post treatment Week 8) ]
    Serum concentrations of daratumumab will be assessed.
  • Number of Participants with Anti-Daratumumab Antibodies [ Time Frame: Arm A: Cycle 1 (each cycle of 28 days) Day 1 (Cycle 1 Day 1), Cycle 3 Day 1; Arm B: Cycle 1 Day1, Cycle 3 Day 1, Cycle 7 Day 1 and Follow Up (post treatment Week 8) ]
    Number of participants who test positive for anti-daratumumab antibodies will be reported.
  • Number of Participants with Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies [ Time Frame: Arm A: Cycle 1 (each cycle of 28 days) Day 1 (Cycle 1 Day 1), Cycle 3 Day 1; Arm B: Cycle 1 Day1, Cycle 3 Day 1, Cycle 7 Day 1 and Follow Up (post treatment Week 8) ]
    Number of participants who test positive for anti-rHuPH20 antibodies will be reported.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab Intravenous (Dara-IV)
Official Title  ICMJE A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination With Carfilzomib and Dexamethasone (DKd) Compared With Carfilzomib and Dexamethasone (Kd) in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab Intravenous (Dara-IV) to Evaluate Daratumumab Retreatment
Brief Summary The purpose of this study is to compare the efficacy (rate of very good partial response [VGPR] or better as best response as defined by the International Myeloma Working Group [IMWG] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab intravenous (Dara-IV) to evaluate daratumumab retreatment.
Detailed Description For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 or 2 prior line(s) of treatment including a line containing Dara-IV to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Carfilzomib 20 mg/m^2
    Carfilzomib 20 mg/m^2 will be administered intravenously (IV).
  • Drug: Carfilzomib 70 mg/m^2
    Carfilzomib 70 mg/m^2 will be administered IV.
  • Drug: Dexamethasone 40 mg
    Dexamethasone 40 mg will be administered as IV infusion or orally.
  • Drug: Dara-SC 1800 mg
    Dara-SC 1800 mg will be administered by SC injection.
  • Drug: Dexamethasone 20 mg
    Dexamethasone 20 mg will be administered as IV infusion or orally.
Study Arms  ICMJE
  • Active Comparator: Arm A: Carfilzomib+Dexamethasone (Kd)
    Participants will receive carfilzomib 20 milligram per square meter (mg/m^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.
    Interventions:
    • Drug: Carfilzomib 20 mg/m^2
    • Drug: Carfilzomib 70 mg/m^2
    • Drug: Dexamethasone 40 mg
    • Drug: Dexamethasone 20 mg
  • Experimental: Arm B: Dara-SC in combination with Kd (DKd)
    Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m^2 IV on Cycle 1 Day 1 and then 70 mg/m^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.
    Interventions:
    • Drug: Carfilzomib 20 mg/m^2
    • Drug: Carfilzomib 70 mg/m^2
    • Drug: Dexamethasone 40 mg
    • Drug: Dara-SC 1800 mg
    • Drug: Dexamethasone 20 mg
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 11, 2019)
230
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 10, 2023
Estimated Primary Completion Date September 14, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to daratumumab-containing intravenously (IV) therapy with response duration of at least 4 months
  • Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or >60 days after cessation of treatment
  • Received 1 or 2 prior line(s) of treatment of which one contained Dara IV, and completed Dara IV at least 3 months prior to randomization. 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 per day [mg/day] for 4 days) would not be considered prior lines of therapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
  • Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Exclusion Criteria:

  • Previous treatment with daratumumab within the last 3 months prior to randomization
  • Discontinuation of Dara IV due to a daratumumab-related adverse event (AE)
  • 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
  • Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
  • Participant is: a) Known to be seropositive for human immunodeficiency virus. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
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: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Belgium,   Brazil,   Canada,   Denmark,   France,   Germany,   Greece,   Italy,   Netherlands,   Poland,   Russian Federation,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03871829
Other Study ID Numbers  ICMJE CR108598
2018-004185-34 ( EudraCT Number )
54767414MMY2065 ( 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
Plan to Share IPD: Yes
Plan Description:

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

URL: https://www.janssen.com/clinical-trials/transparency
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 January 2020

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