An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD

June 21, 2018 updated by: Janssen Research & Development, LLC

An Open-label, Multicenter, Phase 2 Trial Investigating the Efficacy and Safety of Daratumumab in Subjects With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor and IMiD) or Are Double Refractory to a Proteasome Inhibitor and an IMiD

The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are double refractory to a PI and an IMiD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
      • Edmonton, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Spain
      • Barcelona, Spain
      • Salamanca N/A, Spain
      • Valencia, Spain
  • United States
    • California
      • Duarte, California, United States
      • Los Angeles, California, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Illinois
      • Chicago, Illinois, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Michigan
      • Detroit, Michigan, United States
    • New Jersey
      • New Brunswick, New Jersey, United States
    • New York
      • New York, New York, United States
    • North Carolina
      • Chapel Hill, North Carolina, United States
      • Charlotte, North Carolina, United States
    • Oregon
      • Portland, Oregon, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Houston, Texas, United States
    • Wisconsin
      • Madison, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Documented multiple myeloma according to protocol-defined criteria
  • Evidence of disease progression on the most recent prior treatment regimen based on International Myeloma Working Group criteria
  • Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
  • Laboratory values and electrocardiogram within protocol-defined parameters at screening

Exclusion Criteria:

  • Received daratumumab or other anti-CD38 therapies previously
  • Nonsecretory multiple myeloma
  • Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
  • Exhibiting clinical signs of meningeal involvement of multiple myeloma
  • Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
  • Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C
  • Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Drug: Daratumumab 16 mg/kg (Part 1)
Daratumumab 16 mg/kg administered at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter by intravenous infusion
Drug: Daratumumab 8 mg/kg (Part 1)
Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion
Drug: Methylprednisolone
Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted
Drug: Acetaminophen
650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
Drug: Diphenhydramine
25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.
Experimental: Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Drug: Methylprednisolone
Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted
Drug: Acetaminophen
650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
Drug: Diphenhydramine
25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.
Drug: Daratumumab (Part 2)
Based on the Part 1 response rate, Group A or B treatment will be selected as the treatment regimen for participants enrolled in Part 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Overall Response
Time Frame: Up to 14.4 Months
Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; 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 FLC levels is required in place of the M-protein criteria.
Up to 14.4 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response
Time Frame: Up to 14.4 Months
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 IMWG criteria. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component (the absolute increase must be >=0.5 g/dL) and/or; urine M-component (the absolute increase must be >=200 mg/24 hours) and/or; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 milligram per deciliter (mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimole per liter [mmol/L]) that can be attributed solely to the plasma cell proliferative disorder.
Up to 14.4 Months
Overall Survival
Time Frame: Approximately 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.
Approximately up to 3 years
Percentage of Participants With Clinical Benefit
Time Frame: Up to 14.4 Months
Clinical benefit rate defined as percentage of participants who achieved minimal response (MR) or better. MR: >=25% but <= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%. If present at baseline 25% to 49% reduction in size of soft tissue plasmacytomas.
Up to 14.4 Months
Time to Response
Time Frame: Up to 14.4 Months
Time to 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).
Up to 14.4 Months
Progression Free Survival
Time Frame: Up to 14.4 Months
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.
Up to 14.4 Months
Time to Disease Progression
Time Frame: Up to 14.4 Months
Time to progression was defined as the number of days from the date of first dose of daratumumab to the date of first record of disease progression.
Up to 14.4 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 27, 2013

Primary Completion (Actual)

January 9, 2015

Study Completion (Actual)

May 30, 2017

Study Registration Dates

First Submitted

July 22, 2013

First Submitted That Met QC Criteria

November 7, 2013

First Posted (Estimate)

November 15, 2013

Study Record Updates

Last Update Posted (Actual)

June 25, 2018

Last Update Submitted That Met QC Criteria

June 21, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR102651
  • 54767414MMY2002 (Other Identifier: Janssen Research & Development, LLC)
  • 2013-000752-18 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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