Clinical trial NCT02918331: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2016-09-28
Enrollment: 7
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Dose limiting toxicity (DLT) to analyze the safety of daratumumab when combined with lenalidomide and dexamethasone
timeFrame: Cycle 1, Day 1 to Day 28
Secondary outcomes:
measure: Rate of Complete Response (CR) or Better
timeFrame: Approximately 3.7 years
measure: Overall Response Rate (ORR)
timeFrame: Approximately 3.7 years
measure: Very good partial response (VGPR) or better (VGPR, CR, or sCR)
timeFrame: Approximately 3.7 years
measure: Minimum Observed Serum Concentration (Cmin)
timeFrame: 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)
measure: Maximum Observed Concentration (Cmax)
timeFrame: 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)
measure: Immunogenicity of daratumumab
timeFrame: 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)
Other outcomes:
Locations:
city: Hiroshima shi
country: Japan
city: Kanazawa
country: Japan
city: Nagoya
country: Japan
city: Osaka
country: Japan
city: Shibuya
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
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.