Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02136134
First received: May 1, 2014
Last updated: March 27, 2015
Last verified: March 2015
  Purpose

The purpose of this study is to assess the effects of administration of daratumumab when combined with VELCADE (bortezomib) and dexamethasone compared with bortezomib and dexamethasone alone, for participants with relapsed or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: Daratumumab
Drug: VELCADE (Bortezomib)
Drug: Dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Percentage of participants with progression-free survival (PFS) [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    PFS is defined as a duration from the date of randomization to either progressive disease or death, whichever occurs first.


Secondary Outcome Measures:
  • Time to disease progression (TTP) [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    TTP is defined as the time from the date of randomization to the date of first documented evidence of progression, as defined in the International Myeloma Working Group (IMWG) criteria.

  • Percentage of Participants With Overall Response [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    The Overall Response is defined a stringent complete response (sCR), complete response, very good partial response (VGPR) or partial response (PR) as per IMWG Criteria.

  • Duration of response [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: No ]
    Duration of response will be calculated from the date of initial documentation of a response to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.

  • Time to Response [ Time Frame: Baseline, up to 9 weeks ] [ Designated as safety issue: No ]
    Time to response is defined as the time from the date of first dose of study treatment to the date of the first documentation of observed response.

  • Percentage of participants with a very good partial response (VGPR) or better [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    VGPR is defined as a greater than 90% reduction in blood myeloma protein (M-protein) plus urine myeloma protein less than 100 mg per 24 hours.

  • Percentage of participants with Minimal Residual Disease (MRD) [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: No ]
    MRD will be assessed in participants who achieve ≥ VGPR by analyzing bone marrow aspiration specimens.

  • Percentage of participants with overall survival (OS) [ Time Frame: Baseline, up to the end of the study, an expected average of 3 years ] [ Designated as safety issue: Yes ]
    OS will be measured from the date of randomization to the date of the participant's death.


Estimated Enrollment: 480
Study Start Date: August 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daratumumab+VELCADE+dexamethasone
Daratumumab, VELCADE and dexamethasone
Drug: Daratumumab
Daratumumab will be administered as an IV infusion at a dose of 16 mg/kg weekly for the first 3 cycles, on Day 1 of Cycles 4-9, and then every 4 weeks thereafter.
Drug: VELCADE (Bortezomib)
VELCADE will be administered at a dose of 1.3 mg/m2 subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle. Eight VELCADE treatment cycles are to be administered.
Other Name: VELCADE
Drug: Dexamethasone
Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 VELCADE treatment cycles.
Active Comparator: VELCADE+dexamethasone
VELCADE and dexamethasone
Drug: VELCADE (Bortezomib)
VELCADE will be administered at a dose of 1.3 mg/m2 subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle. Eight VELCADE treatment cycles are to be administered.
Other Name: VELCADE
Drug: Dexamethasone
Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 VELCADE treatment cycles.

Detailed Description:

This is an open-label (physicians and participants know the identity of the assigned treatment), randomized (the study medication is assigned by chance), multicenter, active-controlled study comparing daratumumab, VELCADE, and dexamethasone (DVd) with VELCADE and dexamethasone (Vd) in participants with relapsed or refractory multiple myeloma. Approximately 480 participants will be randomly assigned in a 1:1 ratio to receive either DVd or Vd. Randomization will be stratified by International Staging System (ISS), number of prior treatment programs (1 vs. 2 or 3 vs. >3), and prior VELCADE treatment ("no" vs. "yes"). Within each stratum, participants will be randomized to one of the treatment groups.The study will consist of a Screening Phase, a Treatment Phase, and a Follow-up Phase. Participants will be treated until disease progression, unacceptable toxicity, or other reasons to discontinue the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have had documented multiple myeloma
  • Must have received at least 1 prior line of therapy for multiple myeloma
  • Must have had documented evidence of progressive disease as defined based on Investigator's determination of response of International Myeloma Working Group (IMWG) criteria on or after their last regimen
  • Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
  • Must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past

Exclusion Criteria:

  • Has received daratumumab or other anti-CD38 therapies previously
  • Is refractory to VELCADE or another PI, like ixazomib and carfilzomib (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy or another PI therapy, like ixazomib and carfilzomib
  • Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
  • Has 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 milligram per day [mg/day] for a maximum of 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM).
  • Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
  • Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02136134

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 163 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02136134     History of Changes
Obsolete Identifiers: NCT01620879
Other Study ID Numbers: CR103995, 2014-000255-85, 54767414MMY3004
Study First Received: May 1, 2014
Last Updated: March 27, 2015
Health Authority: United States: Food and Drug Administration
Brazil: National Health Surveillance Agency
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut
Mexico: Federal Commission for Sanitary Risks Protection
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Plasmacytoma
Refractory Multiple Myeloma
Relapsed Multiple Myeloma
Daratumumab
VELCADE

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Antibodies, Monoclonal
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on May 28, 2015