A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT01998971
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and dose regimen of daratumumab when administered in combination with various treatment regimens for the treatment of multiple myeloma.
- Detailed Description
This is an open-label (identity of assigned study drug will be known) study to evaluate the safety, tolerability, and dose of daratumumab when administered in combination with various treatment regimens for different settings of multiple myeloma. The various treatment regimens to be combined with daratumumab in this study include Velcade-dexamethasone (VD), Velcade-melphalan-prednisone (VMP), Velcade-thalidomide-dexamethasone (VTD), pomalidomide-dexamethasone (Pom-dex), carfilzomib-dexamethasone (CFZ-dex) and carfilzomib-lenalidomide-dexamethasone (KRd). Approximately 250 patients (approximately 12 participants per VTD and VMP backbone treatment regimen, 6 for the VD regimen, up to 100 participants in the Pom-dex regimen, 80 for the CFZ-dex regimen \[10 participants will receive a single-dose of daratumumab and the remaining participants will receive a split-dose of daratumumab\], and up to 40 for the KRd regimen) will be enrolled in this study. The study will consist of screening, treatment, and follow-up phases. Treatment will extend to either the planned treatment duration for a maximum of 1 year (in Velcade-dexamethasone, Velcade-melphalan-prednisone, Velcade-thalidomide-dexamethasone regimens and KRd regimens), or in the Pom-dex and CFZ-dex regimens, until disease progression, unacceptable toxicity, or until the end of study. Follow-up will continue until the study ends (approximately 25 months after the last patient receives the first dose of daratumumab). Serial pharmacokinetic (study of what a drug does to the body) blood samples will be collected. Clinical efficacy outcomes and safety will be monitored throughout the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 240
- Confirmed diagnosis of symptomatic multiple myeloma and measurable secretory disease
- For carfilzomib-lenalidomide-dexamethasone (KRd) regimen: newly diagnosed myeloma. For carfilzomib-dexamethasone (CFZ-dex) regimen: relapsed or refractory disease
- Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
- Pretreatment clinical laboratory values must meet protocol-defined parameters during the screening phase
- Previously received daratumumab or other anti-CD38 therapies
- Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
- Peripheral neuropathy or neuropathic pain Grade 2 or higher
- Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of study start
- Exhibiting clinical signs of meningeal involvement of multiple myeloma
- Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 2 years
- Seropositive for human immunodeficiency virus, hepatitis B, or hepatitis C
- Any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
- Clinically significant cardiac disease
- Plasma cell leukemia or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Daratumumab + VMP Velcade Daratumumab will be administered with Velcade-melphalan-prednisone (VMP). Daratumumab + VD Velcade Daratumumab will be administered with Velcade-dexamethasone (VD). Daratumumab + VD Acetaminophen Daratumumab will be administered with Velcade-dexamethasone (VD). Daratumumab + VTD Thalidomide Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD). Daratumumab + Pom-dex Diphenhydramine Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex). Daratumumab + VTD Daratumumab Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD). Daratumumab + VTD Velcade Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD). Daratumumab + Pom-dex Pomalidomide Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex). Daratumumab + Pom-dex Daratumumab Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex). Daratumumab + VMP Diphenhydramine Daratumumab will be administered with Velcade-melphalan-prednisone (VMP). Daratumumab + VMP Acetaminophen Daratumumab will be administered with Velcade-melphalan-prednisone (VMP). Daratumumab + VTD Dexamethasone Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD). Daratumumab + CFZ-dex Acetaminophen Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen. Daratumumab + KRd Daratumumab Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen. Daratumumab + VD Daratumumab Daratumumab will be administered with Velcade-dexamethasone (VD). Daratumumab + VD Diphenhydramine Daratumumab will be administered with Velcade-dexamethasone (VD). Daratumumab + VD Dexamethasone Daratumumab will be administered with Velcade-dexamethasone (VD). Daratumumab + VMP Daratumumab Daratumumab will be administered with Velcade-melphalan-prednisone (VMP). Daratumumab + VMP Prednisone Daratumumab will be administered with Velcade-melphalan-prednisone (VMP). Daratumumab + VMP Melphalan Daratumumab will be administered with Velcade-melphalan-prednisone (VMP). Daratumumab + VTD Diphenhydramine Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD). Daratumumab + VTD Acetaminophen Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD). Daratumumab + Pom-dex Acetaminophen Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex). Daratumumab + Pom-dex Dexamethasone Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex). Daratumumab + CFZ-dex Daratumumab Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen. Daratumumab + CFZ-dex Dexamethasone Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen. Daratumumab + KRd Acetaminophen Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen. Daratumumab + CFZ-dex Diphenhydramine Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen. Daratumumab + CFZ-dex Carfilzomib Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen. Daratumumab + CFZ-dex Montelukast Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen. Daratumumab + KRd Diphenhydramine Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen. Daratumumab + KRd Dexamethasone Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen. Daratumumab + KRd Carfilzomib Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen. Daratumumab + KRd Lenalidomide Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen. Daratumumab + KRd Montelukast Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
- Primary Outcome Measures
Name Time Method Number of participants affected by dose-limiting toxicities Up to 30 days after the last dose of study medication Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) Up to 30 days after the last dose of study medication
- Secondary Outcome Measures
Name Time Method Maximum observed concentration of daratumumab Up to post-treatment visit Week 9 Complete response rate Up to 25 months after last patient receives first dose of study drug Overall response rate Up to 25 months after last patient receives first dose of study drug Duration of response Up to 25 months after last patient receives first dose of study drug Number of participants with generation of antibodies to daratumumab Up to post-treatment visit Week 9