Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma

NCT01615029 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: CR101391DARA-GEN5032011-005709-62
• Study Type: interventional
• Target: 45
• Locations: 5 countries
• Sites: 8

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).

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Daratumumab; Lenalidomide; Dexamethasone; Dose-escalation; Relapsed multiple myeloma; Relapsed and refractory multiple myeloma

Outcome Measures

Primary Outcomes (2)

• Phase 1: Percentage of Participants With Overall Response Rate (ORR)

  ORR is defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). International Myeloma Working Group (IMWG) criteria (2011)- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (\<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (\>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90 percentage (%) or to \<200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hour.

  Up to 3 years

• Phase 2: Percentage of Participants With Overall Response Rate (ORR)

  ORR is 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 (2011)- CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (\<) 5 percentage (%) plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: greater than eqaul to (\>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90 percentage (%) or to \<200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hour.

  Up to 3 years

Secondary Outcomes (6)

• Phase 2: Duration of Response

  Up to 5 years

• Phase 1: Time to Response

  Up to 5 years

• Phase 2: Time to Response

  Up to 5 years

• Phase 2: Time to Progression (TTP)

  Up to 5 years

• Phase 2: Progression-Free Survival (PFS)

  Up to 5 years

Study Arms (1)

Daratumumab

EXPERIMENTAL

Participants will receive daratumumab along with Lenalidomide and dexamethasone.

Drug: Part 1 (Dose Escalation): Daratumumab; Drug: Part 2 (Dose Expansion): Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Part 1 (Dose Escalation): Daratumumab DRUG

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.

Daratumumab

Part 2 (Dose Expansion): Daratumumab DRUG

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.

Daratumumab

Lenalidomide DRUG

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.

Daratumumab

Dexamethasone DRUG

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.

Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (8)

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Copenhagen Ø, Denmark

Location

Unknown Facility

Vejle, Denmark

Location

Unknown Facility

Lille, France

Location

Unknown Facility

Nantes, France

Location

Unknown Facility

Vandœuvre-lès-Nancy, France

Location

Unknown Facility

Utrecht, Netherlands

Location

Unknown Facility

London, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 29025767 DERIVED

• 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.

  PMID: 27531679 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Senior Director, Clinical Research
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

• Torben Plesner, MD

  Vejle Hospital

  PRINCIPAL INVESTIGATOR

• Paul Richardson, MD

  Dana Farber

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 8, 2012
• Study Start: June 26, 2012
• Primary Completion: October 2, 2015
• Study Completion: October 23, 2024
• Last Updated: March 16, 2026
• Results First Posted: April 14, 2017

Record last verified: 2026-03

Locations

FR (3); NL (1); GB (1); DK (2); US (1)