Clinical trial NCT01615029: Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Daratumumab
Lenalidomide
Dexamethasone
Dose-escalation
Relapsed multiple myeloma
Relapsed and refractory multiple myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-06-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Up to 3 years
measure: Phase 2: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Phase 2: Time to Progression (TTP)
timeFrame: Up to 3 years
measure: Phase 2: Duration of Response
timeFrame: Up to 3 years
measure: Phase 2: Progression-Free Survival (PFS)
timeFrame: Up to 3 years
measure: Phase 1: Time to Response
timeFrame: Up to 3 years
measure: Phase 2: Time to Response
timeFrame: Up to 3 years
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Boston
country: United States
state: Massachusetts
city: Copenhagen Ø
country: Denmark
city: Vejle
country: Denmark
city: Lille Cedex
country: France
city: Nantes N/a
country: France
city: Vandoeuvre les Nancy
country: France
city: Utrecht
country: Netherlands
city: London
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
affiliation: Vejle Hospital
name: Torben Plesner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana Farber
name: Paul Richardson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Krejcik J, Frerichs KA, Nijhof IS, van Kessel B, van Velzen JF, Bloem AC, Broekmans MEC, Zweegman S, van Meerloo J, Musters RJP, Poddighe PJ, Groen RWJ, Chiu C, Plesner T, Lokhorst HM, Sasser AK, Mutis T, van de Donk NWCJ. Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab. Clin Cancer Res. 2017 Dec 15;23(24):7498-7511. doi: 10.1158/1078-0432.CCR-17-2027. Epub 2017 Oct 12.
citation: Plesner T, Arkenau HT, Gimsing P, Krejcik J, Lemech C, Minnema MC, Lassen U, Laubach JP, Palumbo A, Lisby S, Basse L, Wang J, Sasser AK, Guckert ME, de Boer C, Khokhar NZ, Yeh H, Clemens PL, Ahmadi T, Lokhorst HM, Richardson PG. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood. 2016 Oct 6;128(14):1821-1828. doi: 10.1182/blood-2016-07-726729. Epub 2016 Aug 16.