An Open-Label, Multicenter, Phase 1b Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Regimens for the Treatment of Subjects With Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 240
- 主要终点
- Number of participants affected by dose-limiting toxicities
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Daratumumab + VD
Daratumumab will be administered with Velcade-dexamethasone (VD).
干预措施: Daratumumab (Drug)
Daratumumab + VD
Daratumumab will be administered with Velcade-dexamethasone (VD).
干预措施: Velcade (Drug)
Daratumumab + VD
Daratumumab will be administered with Velcade-dexamethasone (VD).
干预措施: Dexamethasone (Drug)
Daratumumab + VD
Daratumumab will be administered with Velcade-dexamethasone (VD).
干预措施: Diphenhydramine (Drug)
Daratumumab + VD
Daratumumab will be administered with Velcade-dexamethasone (VD).
干预措施: Acetaminophen (Drug)
Daratumumab + VMP
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
干预措施: Daratumumab (Drug)
Daratumumab + VMP
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
干预措施: Velcade (Drug)
Daratumumab + VMP
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
干预措施: Melphalan (Drug)
Daratumumab + VMP
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
干预措施: Prednisone (Drug)
Daratumumab + VMP
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
干预措施: Diphenhydramine (Drug)
Daratumumab + VMP
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
干预措施: Acetaminophen (Drug)
Daratumumab + VTD
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
干预措施: Daratumumab (Drug)
Daratumumab + VTD
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
干预措施: Velcade (Drug)
Daratumumab + VTD
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
干预措施: Dexamethasone (Drug)
Daratumumab + VTD
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
干预措施: Thalidomide (Drug)
Daratumumab + VTD
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
干预措施: Diphenhydramine (Drug)
Daratumumab + VTD
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
干预措施: Acetaminophen (Drug)
Daratumumab + Pom-dex
Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).
干预措施: Acetaminophen (Drug)
Daratumumab + Pom-dex
Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).
干预措施: Daratumumab (Drug)
Daratumumab + Pom-dex
Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).
干预措施: Pomalidomide (Drug)
Daratumumab + Pom-dex
Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).
干预措施: Dexamethasone (Drug)
Daratumumab + Pom-dex
Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).
干预措施: Diphenhydramine (Drug)
Daratumumab + CFZ-dex
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
干预措施: Daratumumab (Drug)
Daratumumab + CFZ-dex
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
干预措施: Dexamethasone (Drug)
Daratumumab + CFZ-dex
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
干预措施: Diphenhydramine (Drug)
Daratumumab + CFZ-dex
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
干预措施: Acetaminophen (Drug)
Daratumumab + CFZ-dex
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
干预措施: Carfilzomib (Drug)
Daratumumab + CFZ-dex
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
干预措施: Montelukast (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Daratumumab (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Dexamethasone (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Diphenhydramine (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Acetaminophen (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Carfilzomib (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Montelukast (Drug)
Daratumumab + KRd
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Number of participants affected by dose-limiting toxicities
时间窗: 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)
时间窗: Up to 30 days after the last dose of study medication
次要结局
- 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)