This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01985126
First received: July 22, 2013
Last updated: March 24, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Multiple Myeloma Drug: Daratumumab 16 mg/kg (Part 1) Drug: Daratumumab 8 mg/kg (Part 1) Drug: Methylprednisolone Drug: Acetaminophen Drug: Diphenhydramine Drug: Daratumumab (Part 2) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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). IMWG criteria- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<)5 percent plasma cells in bone marrow; sCR: CR+Normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: greater than or equal to (>=) 50 percent reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percent; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90 percent or greater reduction in serum M-protein plus urine M-protein level less than (<) 100 milligram (mg) per 24 hour.


Secondary Outcome Measures:
  • 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 [>= 50 percent reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percent] or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.

  • Overall Survival [ Time Frame: Up to 14.4 Months ]
    Overall survival was defined as the time from the date of first dose of daratumumab to the date of the partcipant's death from any cause.

  • Percentage of Participants With Clinical Benefit [ Time Frame: Up to 14.4 Months ]
    Clinical benefit rate was defined as the percentage of participants with best response of minimal response (MR) or better (including PR [>= 50 percent reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percent], VGPR [Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90 percent or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour], CR [Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 percent plasma cells in bone marrow], and sCR [CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence]).

  • 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 [>= 50 percent reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percent] or better).

  • Progression Free Survival [ Time Frame: Up to 14.4 Months ]
    Progression free survival was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurred first. Disease progression as per IMWG criteria: increase of >=25 percent from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL) Urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase must be >10 mg/dL; Bone marrow plasma cell percentage: the absolute percent must be >=10 percent; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

  • 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.


Enrollment: 124
Actual Study Start Date: September 27, 2013
Estimated Study Completion Date: June 30, 2017
Primary Completion Date: January 9, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01985126

  Show 23 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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01985126     History of Changes
Other Study ID Numbers: CR102651
54767414MMY2002 ( Other Identifier: Janssen Research & Development, LLC )
2013-000752-18 ( EudraCT Number )
Study First Received: July 22, 2013
Results First Received: September 30, 2016
Last Updated: March 24, 2017

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Janssen Research & Development, LLC:
Multiple myeloma
Daratumumab
Proteasome inhibitor
Immunomodulatory drug
IMiD

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Acetaminophen
Diphenhydramine
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Daratumumab
Promethazine
Antibodies, Monoclonal
Proteasome Inhibitors
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on June 26, 2017