Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Lenalidomide

Daratumumab

Dexamethasone acetate

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Participants will receive daratumumab along with Lenalidomide and dexamethasone.

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 1 (Dose Escalation): 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.

Part 2 (Dose Expansion): Daratumumab

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.

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.

Janssen Research & Development, LLC Clinical Trial

Torben Plesner, MD

Paul Richardson, MD

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).

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.

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

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

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- 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.

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- 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.

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.

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.

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.

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.

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.

Janssen Research & Development, LLC

Participants administered with daratumumab 2 milligram/kilogram (mg/kg) on Day 0 (pre dose infusion), 1, 8, 15, 22 (cycle 1), Days 1, 8, 15, and 22 (cycle 2), Days 1 and 15 (Cycles 3 to 6), Day 1 (Cycle 7+) along with Lenalidomide 25 milligram (mg) on Day 1 to 21 of each 28-day cycle and Dexamethasone 40 mg (weekly) and may be reduced to 20 mg (weekly after cycle 6 at the investigator's discretion). Each treatment cycle consists of 28 days.

Phase 1: 2 mg/kg Daratumumab + Lenalidomide and Dexamethasone

Participants administered with daratumumab 4 mg/kg on Day 0 (pre dose infusion), 1, 8, 15, 22 (cycle 1), Days 1, 8, 15, and 22 (cycle 2), Days 1 and 15 (Cycles 3 to 6), Day 1 (Cycle 7+) along with Lenalidomide 25 milligram (mg) on Day 1 to 21 of each 28-day cycle and Dexamethasone 40 mg (weekly) and may be reduced to 20 mg (weekly after cycle 6 at the investigator's discretion). Each treatment cycle consists of 28 days.

Phase 1: 4 mg/kg Daratumumab + Lenalidomide and Dexamethasone

Participants administered with daratumumab 8 mg/kg on Day 0 (pre dose infusion), 1, 8, 15, 22 (cycle 1), Days 1, 8, 15, and 22 (cycle 2), Days 1 and 15 (Cycles 3 to 6), Day 1 (Cycle 7+) along with Lenalidomide 25 milligram (mg) on Day 1 to 21 of each 28-day cycle and Dexamethasone 40 mg (weekly) and may be reduced to 20 mg (weekly after cycle 6 at the investigator's discretion). Each treatment cycle consists of 28 days.

Phase 1: 8mg/kg Daratumumab + Lenalidomide and Dexamethasone

Participants administered with daratumumab 16 mg/kg on Day 0 (pre dose infusion), 1, 8, 15, 22 (cycle 1), Days 1, 8, 15, and 22 (cycle 2), Days 1 and 15 (Cycles 3 to 6), Day 1 (Cycle 7+) along with Lenalidomide 25 milligram (mg) on Day 1 to 21 of each 28-day cycle and Dexamethasone 40 mg (weekly) and may be reduced to 20 mg (weekly after cycle 6 at the investigator's discretion). Each treatment cycle consists of 28 days.

Phase 1: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone

Participants administered with daratumumab 16 mg/kg on Day 1, 8, 15, 22 (cycle 1), Days 1, 8, 15, and 22 (cycle 2), Days 1 and 15 (Cycles 3 to 6), Day 1 (Cycle 7+) along with Lenalidomide 25 milligram (mg) on Day 1 to 21 of each 28-day cycle and Dexamethasone 40 mg (weekly) and may be reduced to 20 mg (weekly after cycle 6 at the investigator's discretion). Each treatment cycle consists of 28 days.

Phase 2: 16 mg/kg Daratumumab + Lenalidomide and Dexamethasone

Total

Age, Continuous

Sex: Female, Male

Denmark

France

Italy

Netherlands

United Kingdom

United States

Region of Enrollment

The International Staging System (ISS) system consists of stage I: beta2 microglobulin less than (\<)3.5 milligram per liter (mg/L) and albumin greater than or equal to (\>=) 3.5 gram/ deciliter (dL) or (35 gram/L); stage II: neither stage I nor stage III and stage III: beta2 microglobulin \>= 5.5 mg/L.

Stage of Disease [International Staging System (ISS)

1 Line

2-3 Lines

>3 Lines

No. of Prior Lines of Therapy

Both a PI and IMiD

PI only

IMiD only

None

Refractory to Proteasome Inhibitor (PI)/Immunomodulatory drug (IMiD)

Senior Director, Clinical Research

Participants administered with daratumumab 8 mg/kg on Day 0 (pre dose infusion), 1, 8, 15, 22 (cycle 1), Days 1, 8, 15, and 22 (cycle 2), Days 1 and 15 (Cycles 3 to 6), Day 1 (Cycle 7+) along with Lenalidomide 25 milligram (mg) on day 1 to 21 of each 28-day cycle and Dexamethasone 40 mg (weekly) and may be reduced to 20 mg (weekly after cycle 6 at the investigator's discretion). Each treatment cycle consists of 28 days.

Phase 1: 8 mg/kg Daratumumab + Lenalidomide and Dexamethasone

All treated analysis set included all enrolled participants who received at least one non-zero dose of any study drug during Phase 1.

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

Intent-to-Treat (ITT) population analysis set included all enrolled participants who signed the informed consent during Phase 2.

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

ITT population analysis set included all enrolled participants who signed the informed consent during Phase 2.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma	NCT01615029	Multiple Myelom...	Part 1 (Dose Es... Part 2 (Dose Ex... Lenalidomide Dexamethasone	18 Years -	Janssen Research & Development, LLC
Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma	NCT01615029	Multiple Myelom...	Part 1 (Dose Es... Part 2 (Dose Ex... Lenalidomide Dexamethasone	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for part 2 (dose expansion): daratumumab