Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments part 1 (dose escalation): daratumumab, part 2 (dose expansion): daratumumab, lenalidomide, dexamethasone
Phase phase 1/phase 2
Sponsor Janssen Research & Development, LLC
Start date January 2012
End date October 2015
Trial size 45 participants
Trial identifier NCT01615029, 2011-005709-62, CR101391, DARA-GEN503, GEN503

Summary

The purpose of this study is to establish the safety profile of daratumumab when given in combination with Lenalidomide and dexamethasone in participants with relapsed or relapsed and refractory Multiple Myeloma (MM).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants will receive daratumumab along with Lenalidomide and dexamethasone.
part 1 (dose escalation): daratumumab
Participants will receive intravenous (injection of a substance into a vein) infusion of daratumumab in an increased fashion from 2 milligram per kilogram (mg/kg) up to maximum dose of 16 mg/kg. Considering the safety and efficacy of dose in Part 1, recommended phase 2 dose (RP2D) for Part 2 of the study will be decided. A predose infusion of 10 percent (%) of the full dose of daratumumab will be administered a day before the first full infusion of the first cycle. Participants will receive 4 weekly infusions in the first 2 treatment cycles. From cycles 3 to 6 infusions will be administered every alternate week and monthly infusions will be administered from cycle 7 until disease progression.
part 2 (dose expansion): daratumumab
Participants will receive RP2D as determined in Part 1 of the study. Participants will receive 4 weekly infusions of RP2D in the first 2 treatment cycles. From cycles 3 to 6 infusions will be administered every alternate week and monthly infusions will be administered from cycle 7 until disease progression.
lenalidomide
All participants (Part 1 and Part 2) will receive 25 mg lenalidomide orally (by mouth) from days 1 to 21 of each 28-day cycle until disease progression.
dexamethasone
All participants (Part 1 and Part 2) will receive 40 mg (20 mg intravenously [injection of a substance into a vein]) dexamethasone once weekly. Participants older than 75 years or underweight (body mass index [BMI] less than [<] 18.5), the dexamethasone dose will be administered at a dose of 20 mg once weekly until disease progression.

Primary Outcomes

Measure
Part 1 and 2: Number of participants with adverse events
time frame: Up to 3 years

Secondary Outcomes

Measure
Part 1 and 2: Number of participants with objective response
time frame: End of the Treatment (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Area under the concentration-time curve of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Maximum observed concentration of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Minimum observed concentration of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Time to reach the maximum plasma concentration of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Apparent clearance of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Volume of distribution of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Half-life of daratumumab
time frame: Predose and up to 12hrs for Cycle 1;predose and up to 2hrs for Cycle 2;predose and end of daratumumab infusion for Cycles 3 to 24;monthly for follow-up visits (up to 6 months);and at end of treatment visit (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Time taken for progression of disease
time frame: End of the Treatment (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Duration of response
time frame: End of the Treatment (3 to 5 Weeks After the Last Dose of Study Drug)
Part 1 and 2: Participants with progression free survival
time frame: End of the Treatment (3 to 5 Weeks After the Last Dose of Study Drug)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - (Part 1) Have relapsed multiple myeloma after receiving a minimum of 2 and a maximum of 4 prior lines of therapy and be eligible for treatment with lenalidomide and dexamethasone (Len/Dex) - (Part 2) Have received at least 1 prior line of therapy for multiple myeloma - Be older than or be 18 years of age - Eastern Cooperative Oncology Group (ECOG) performance status (0-2) - Provide signed informed consent after receipt of oral and written information about the study and before any study-related activity is performed Exclusion Criteria: - Have previously received an allogenic stem cell transplant - Have received autologous stem cell transplant within 12 weeks before the first infusion - Have received antimyeloma treatment, radiotherapy, or any experimental drug or therapy within 2 weeks before the first infusion - Have discontinued lenalidomide due to any treatment-related adverse event or be refractory to any dose of lenalidomide. Refractory to lenalidomide is defined as either, participants whose disease progresses within 60 days of lenalidomide, or participants whose disease is nonresponsive while on any dose of lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an minimal response (MR) or development of progressive disease (PD) while on lenalidomide

Additional Information

Official title An Open Label, International, Multicenter, Dose Escalating Phase I/II Trial Investigating the Safety of Daratumumab in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Relapsed and Refractory Multiple Myeloma
Principal investigator Torben Plesner, MD
Description The study is conducted in two parts. The dose escalation portion of the trial (Part 1) participants are enrolled into cohorts at increasing dose levels of daratumumab in combination with Len/Dex in 28 day treatment cycles. Part 2, the cohort expansion part of the trial, will further explore the maximum tolerated dose (MTD) (or the maximum tested dose) of daratumumab as determined in Part 1.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Janssen Research & Development, LLC.