A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Acetaminophen; Drug: Melphalan; Drug: Lenalidomide; Drug: Pomalidomide; Drug: Velcade; Drug: Diphenhydramine; Drug: Dexamethasone; Drug: Daratumumab; Drug: Montelukast; Drug: Thalidomide; Drug: Prednisone; Drug: Carfilzomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01998971

54767414MMY1001 (Other Identifier)

2013-003491-12 (EudraCT Number)

CR103015

Details and patient eligibility

About

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.

Full 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.

Enrollment: 240 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 6 patient groups

Daratumumab + VD

Experimental group

Description:

Daratumumab will be administered with Velcade-dexamethasone (VD).

Treatment:

Drug: Daratumumab

Drug: Dexamethasone

Drug: Diphenhydramine

Drug: Velcade

Drug: Acetaminophen

Daratumumab + VMP

Experimental group

Description:

Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).

Treatment:

Drug: Daratumumab

Drug: Diphenhydramine

Drug: Velcade

Drug: Prednisone

Drug: Melphalan

Drug: Acetaminophen

Daratumumab + VTD

Experimental group

Description:

Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).

Treatment:

Drug: Daratumumab

Drug: Dexamethasone

Drug: Diphenhydramine

Drug: Velcade

Drug: Thalidomide

Drug: Acetaminophen

Daratumumab + Pom-dex

Experimental group

Description:

Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).

Treatment:

Drug: Daratumumab

Drug: Dexamethasone

Drug: Diphenhydramine

Drug: Pomalidomide

Drug: Acetaminophen

Daratumumab + CFZ-dex

Experimental group

Description:

Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.

Treatment:

Drug: Daratumumab

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Diphenhydramine

Drug: Montelukast

Drug: Acetaminophen

Daratumumab + KRd

Experimental group

Description:

Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.

Treatment:

Drug: Daratumumab

Drug: Carfilzomib

Drug: Dexamethasone

Drug: Diphenhydramine

Drug: Montelukast

Drug: Lenalidomide

Drug: Acetaminophen