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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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

Daratumumab (16 mg/kg)

Lenalidomide

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Daratumumab with Lenalidomide and dexamethasone

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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).

Minimum Observed Serum Concentration (Cmin)

The Cmin is the minimum observed analyte concentration.

Maximum Observed Concentration (Cmax)

The Cmax is the maximum observed analyte concentration.

Immunogenicity of daratumumab

Anti-daratumumab antibodies will be evaluated in serum samples collected for all the participants.

Full Information

NCT ID

NCT02918331

First Posted

September 27, 2016

Last Updated

April 2, 2020

Sponsor

Janssen Pharmaceutical K.K.

1. Study Identification

Unique Protocol Identification Number

NCT02918331

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

September 2016 (Actual)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

March 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Pharmaceutical K.K.

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Daratumumab with Lenalidomide and dexamethasone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Daratumumab (16 mg/kg)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

Participants will receive dexamethasone 40 mg weekly, at day 1, 8, 15, 22 of each cycle.

Primary Outcome Measure Information:

Title

Dose limiting toxicity (DLT) to analyze the safety of daratumumab when combined with lenalidomide and dexamethasone

Description

Number of Participants With Dose Limiting Toxicity During Cycle 1.

Time Frame

Cycle 1, Day 1 to Day 28

Secondary Outcome Measure Information:

Title

Rate of Complete Response (CR) or Better

Description

CR is Defined as the proportion of Participants achieving CR (including stringent complete response [sCR]) according to the International Myeloma Working Group (IMWG) criteria.

Time Frame

Approximately 3.7 years

Title

Overall Response Rate (ORR)

Description

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.

Time Frame

Approximately 3.7 years

Title

Very good partial response (VGPR) or better (VGPR, CR, or sCR)

Description

Time Frame

Approximately 3.7 years

Title

Minimum Observed Serum Concentration (Cmin)

Description

The Cmin is the minimum observed analyte concentration.

Time Frame

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)

Title

Maximum Observed Concentration (Cmax)

Description

The Cmax is the maximum observed analyte concentration.

Time Frame

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)

Title

Immunogenicity of daratumumab

Description

Anti-daratumumab antibodies will be evaluated in serum samples collected for all the participants.

Time Frame

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Pharmaceutical K.K., Japan Clinical Trial

Organizational Affiliation

Janssen Pharmaceutical K.K.

Official's Role

Study Director

Facility Information:

City

Hiroshima

Country

Japan

City

Kanazawa

Country

Japan

City

Nagoya

Country

Japan

City

Osaka

Country

Japan

City

Shibuya

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

32002821

Citation

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.

Results Reference

derived

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