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Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00574288
First Posted: December 17, 2007
Last Update Posted: July 12, 2017
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.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
December 14, 2007
December 17, 2007
October 21, 2016
March 9, 2017
July 12, 2017
March 26, 2008
January 9, 2015   (Final data collection date for primary outcome measure)
  • Number of Participants With Adverse Events [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 27 (for Part 2) ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
  • Percentage of Participants With Overall Response Rate [ Time Frame: Up to Week 28 (for Part 1) and Week 27 (for Part 2) ]
    Overall response defined as percentage of participants who achieved complete response (CR), very good partial response (VGPR) or partial response (PR). Per 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; PR: greater than or equal to (>=) 50 percent reduction of serum M-protein and reduction in 24hour 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.
Adverse events measured throughout the study from first treatment visit (visit 2) until end of trial (potentially 2 y after first treatment). [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00574288 on ClinicalTrials.gov Archive Site
  • Part 1: Median Time to Response [ Time Frame: Up to Week 28 ]
    Time to first 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). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response.
  • Part 2: Median Time to Progression (TTP) [ Time Frame: Up to Week 27 ]
    TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (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 % must be >=10 %; 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. Median TTP was estimated by using the Kaplan-Meier method.
  • Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier [ Time Frame: Up to Week 27 ]
    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 the International Myeloma Working Group (IMWG) criteria.
  • Part 2: Median Progression-Free Survival [ Time Frame: Up to Week 27 ]
    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.
  • Part 2: Time to Response [ Time Frame: Up to Week 27 ]
    Time to first 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). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. VGPR: serum and urine M-protein detected by immunofixation but not electrophoresis, greater than (>) 90 percent in serum M-protein+urine, M-protein level less than (<) 100 milligram per 24 hour (mg/24hour). The Kaplan-Meier method was used to estimate time to response.
  • Part 2: Median Overall Survival [ Time Frame: Up to Week 27 ]
    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.
PK parameters based on serum/plasma conc. of HuMax-CD38. Objective response according to International uniform response criteria for MM. Relative reduction in M-component. Time to progression. Duration of response. [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma
Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma - Open Label, Dose-escalation Followed by Open Label, Single-arm Study
Establishment of safety profile of HuMax-CD38 when given as monotherapy in participants with multiple myeloma relapsed from or refractory to at least 2 different cytoreductive therapies and without further established treatment options.
This study is conducted in two parts. In part I, participants are enrolled into cohorts at increasing dose levels. Participant safety and efficacy during part I will determine the doses used for Part II. In part II participants will be enrolled into one of two sequential treatment arms using two of the doses defined in part 1 of the study. Part II was 5 cohorts, 3 with 8 milligram per kilogram (mg/kg) and 2 with 16 mg/kg. Part I and all but the last cohort in Part II were dosed with Phase 1/ 2 drug product. The last cohort in Part II was dosed with Phase 3 drug product. Both Part I and Part II are open-label/unmasked.
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Part 1: Daratumumab
    First participant will receive intravenous (injection of a substance into a vein) 0.005 milligram per kilogram (mg/kg) (planned dose) infusion of daratumumab and other participants will receive different doses. The participants will receive 7 full infusions of daratumumab and 2 predose infusions every 2 weeks. The dose of daratumumab will be escalated sequentially and considering the safety and efficacy of dose in Part 1, dose for Part 2 of the study will be decided. A predose infusion of 10% of the full dose of daratumumab will be administered a day before the first 2 full infusions.
    Other Name: HuMax-CD38
  • Drug: Part 2: Daratumumab
    In Part 2, the participants will receive dose of daratumumab as determined in part 1 (16 mg/kg) of the study. Participants will receive 8 full infusions at weekly intervals followed by biweekly (every 2 weeks) infusions for 16 additional weeks and monthly infusions until disease progression or unmanageable toxicity, whichever comes first. Predose was dropped at some point in Part 2. A predose infusion of 10 mg daratumumab will be administered on the day before the first full infusion in select cohorts.
    Other Name: HuMax-CD38
  • Other: Methylprednisolone

    Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4.

    Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions.

  • Other: Dexamethasone
    Participants (Part 2) will receive 20 mg dexamethasone intravenous (IV) injection pre-dose, on the first and second days after every full-dose infusions.
  • Experimental: Dose Escalation: Daratumumab
    Interventions:
    • Drug: Part 1: Daratumumab
    • Other: Methylprednisolone
  • Experimental: Dose Expansion: Daratumumab
    Interventions:
    • Drug: Part 2: Daratumumab
    • Other: Methylprednisolone
    • Other: Dexamethasone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
104
March 29, 2017
January 9, 2015   (Final data collection date for primary outcome measure)

Inclusion criteria

  • Diagnosis of multiple myeloma (MM) requiring systemic therapy
  • Age greater than or equal to (>=) 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Life expectancy greater than (>) 3 months
  • Relapsed from or refractory to two or more different prior therapies
  • Signed Informed consent

Exclusion criteria

  • Plasma cell leukemia defined as a plasma cell count > 2000/millimeter^3 (mm^3)
  • Known amyloidosis
  • Participants who previously have received an allogeneic stem cell transplant
  • Sensory or motor neuropathy of >= grade 3
  • Past or current malignancy
  • Chronic or ongoing active infectious disease
  • Clinically significant cardiac disease
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal (except related to MM), hepatic, hematological except MM, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
  • A baseline QT interval as corrected by Fridericia's formula > 470 millisecond (msec) for female participants or > 450 msec for male participants or a complete left bundle branch block (defined as a QRS interval >= 120 msec in left bundle branch block form)
  • Hypokalemia
  • Clinical signs of meningeal involvement of MM
  • Known severe chronic obstructive pulmonary disease or asthma defined as forced expiratory volume in 1 second (FEV1) less than (<) 60 percentage (%) of expected
  • History of significant cerebrovascular disease
  • Known Human Immunodeficiency Virus seropositivity
  • Positive serology for hepatitis B
  • Screening laboratory values
  • Concomitant corticosteroid
  • Other chemotherapy that is or may be active against myeloma within 3 weeks prior to Visit 2 (Part 1) or the first dose of daratumumab (Part 2). However, corticosteroid for myeloma (less than a 4-day course) could be administered within 1 week before Visit 2 (Part 1) or the first dose of daratumumab (Part 2)
  • Known hypersensitivity to components of the investigational product or severe allergic or anaphylactic reactions to humanized products
  • Participants who have received treatment with any nonmarket drug substance within 4 weeks before the first dose of daratumumab
  • Current participation in any other interventional clinical trial
  • Participants known or suspected of not being able to comply with a trial protocol (example, due to alcoholism, drug dependency, or psychological disorder)
  • Breastfeeding women or women with a positive pregnancy test at Screening
  • Women of childbearing potential not willing to use adequate contraception, defined as hormonal birth control or intrauterine device, during the trial and for 1 year after the last dose of daratumumab. For participants in the United States, the use of a double-barrier method is also considered adequate
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Denmark,   Netherlands,   Sweden,   United States
 
 
NCT00574288
CR101876
GEN501 ( Other Identifier: Janssen Research & Development, LLC )
DARA-GEN501 ( Other Identifier: Janssen Research & Development, LLC )
2007-003783-22 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Not Provided
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
June 2017

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