A Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone in Japanese Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation

A Phase 1b Study of JNJ-54767414 (Daratumumab) in Combination With Lenalidomide and Dexamethasone (DRd) in Japanese Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy and Autologous Stem Cell Transplantation

The purpose of this study is to evaluate the safety of daratumumab when combined with lenalidomide and dexamethasone in Japanese participants with newly diagnosed multiple myeloma who are not candidates for high-dose chemotherapy and autologous stem cell transplantation (ASCT).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Daratumumab (16 mg/kg); Drug: Lenalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Hiroshima, Japan
  • Kanazawa, Japan
  • Nagoya, Japan
  • Osaka, Japan
  • Shibuya, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with documented multiple myeloma (MM) satisfying the CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities) criteria , monoclonal plasma cells in the bone marrow more than equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable disease Measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G MM: serum monoclonal paraprotein (M protein) level >=1.0 gram/deciliter (dL) or urine M protein level >= 200 milligram(mg)/24 hours; or (b) IgA, IgM, IgD, or IgE MM: serum M protein level >=0.5 g/dL or urine M protein level >=200 mg/24 hours; or (c) Light chain MM without measurable disease in serum or urine: serum Ig free light chain (FLC) >=10 mg/dL and abnormal serum Ig kappa lambda FLC ratio
• Participants newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to being >=65 years old, or in subjects less than (<) 65 years old presence of important comorbid condition(s) likely to have a negative effect on the tolerability of high-dose chemotherapy with ASCT
• Pretreatment clinical laboratory values meeting the following criteria during the Screening Phase
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 4 weeks prior to dosing and the second within 3 days prior to dosing

Exclusion Criteria:

• Participants with diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering MM
• Participant with plasma cell leukemia or other conditions in which Ig (immunoglobulin) M protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
• Participants who have prior or current systemic therapy or ASCT for MM, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment
• Participants with history of malignancy (other than MM) within 5 years before the date of the first daratumumab administration
• Participants who have radiation therapy within 14 days of the first dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Daratumumab with Lenalidomide and dexamethasone; Daratumumab (16 milligram per kilogram [mg/kg]) will be administered by intravenous [IV] infusion to all participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity or study end. Participants will receive lenalidomide 25 mg orally on Days 1 through 21 of each 28 day cycle. Participants will receive dexamethasone 40mg weekly, at day 1, 8, 15, 22 of each cycle.

Drug: Daratumumab (16 mg/kg); Daratumumab (16 mg/kg) will be administered by IV infusion to all participants once every week for 8 weeks; then once every other week for 16 weeks; thereafter once every 4 weeks until documented progression, unacceptable toxicity or study end.; Drug: Lenalidomide; Participants will receive lenalidomide 25 mg orally on Days 1 through 21 of each 28 day cycle. Participants with creatinine clearance (CrCl) between 30 and 60 milliLitre (mL)/minute (min) will receive lenalidomide 10 mg every 24 hours.; Drug: Dexamethasone; Participants will receive dexamethasone 40 mg weekly, at day 1, 8, 15, 22 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT) to analyze the safety of daratumumab when combined with lenalidomide and dexamethasone	Number of Participants With Dose Limiting Toxicity During Cycle 1.	Cycle 1, Day 1 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Complete Response (CR) or Better	CR is Defined as the proportion of Participants achieving CR (including stringent complete response [sCR]) according to the International Myeloma Working Group (IMWG) criteria.	Approximately 3.7 years
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve CR, Partial Response (PR), VGPR, and sCR according to the IMWG criteria, during or after study treatment.	Approximately 3.7 years
Very good partial response (VGPR) or better (VGPR, CR, or sCR)	VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 pecent (%) reduction in serum M-protein plus urine M-protein level less than (<) 100 milligram(mg)/24 hour (h).	Approximately 3.7 years
Minimum Observed Serum Concentration (Cmin)	The Cmin is the minimum observed analyte concentration.	Cycle 1, Cycle 3, Cycle 6, Cycle 12 (each cycle of 28 days), End of Treatment (within 30 days of the last dose), and Follow-Up (8 weeks after the last dose)
Maximum Observed Concentration (Cmax)	The Cmax is the maximum observed analyte concentration.	Cycle 1, Cycle 3, Cycle 6, Cycle 12 (each cycle of 28 days), End of Treatment (within 30 days of the last dose), and Follow-Up (8 weeks after the last dose)
Immunogenicity of daratumumab	Anti-daratumumab antibodies will be evaluated in serum samples collected for all the participants.	Cycle 1, Cycle 3, Cycle 12 (each cycle of 28 days), End of Treatment (within 30 days of the last dose), and Follow-Up (8 weeks after the last dose)

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Publications and helpful links

General Publications

• Takamatsu H, Iida S, Shibayama H, Shibayama K, Yamazaki H, Suzuki K. Daratumumab, lenalidomide, and dexamethasone in Japanese patients with transplant-ineligible newly diagnosed multiple myeloma: a phase 1b study. Int J Hematol. 2020 May;111(5):692-701. doi: 10.1007/s12185-020-02825-w. Epub 2020 Jan 30.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimate): September 28, 2016

Study Record Updates

• Last Update Posted (Actual): April 3, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Daratumumab
• Other Study ID Numbers: CR108197; 54767414MMY1006 (Other Identifier: Janssen Pharmaceutical K.K., Japan)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No