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

NCT ID: NCT01615029

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-26
• Study Completion Date: 2024-10-23

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Daratumumab

Participants will receive daratumumab along with Lenalidomide and dexamethasone.

Group Type: EXPERIMENTAL

Part 1 (Dose Escalation): Daratumumab

Intervention Type: 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.

Part 2 (Dose Expansion): Daratumumab

Intervention Type: 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.

Lenalidomide

Intervention Type: 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.

Dexamethasone

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Torben Plesner, MD

Role: PRINCIPAL_INVESTIGATOR

Vejle Hospital

Paul Richardson, MD

Role: PRINCIPAL_INVESTIGATOR

Dana Farber

Locations

Boston, Massachusetts, United States

Copenhagen Ø, , Denmark

Vejle, , Denmark

Lille, , France

Nantes, , France

Vandœuvre-lès-Nancy, , France

Utrecht, , Netherlands

London, , United Kingdom

Countries

United States; Denmark; France; Netherlands; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29025767 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27531679 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

DARA-GEN503

Identifier Type: OTHER

Identifier Source: secondary_id

2011-005709-62

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR101391

Identifier Type: -

Identifier Source: org_study_id