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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01998971
• Other study ID #: CR103015
• Secondary ID: 54767414MMY10012
• Status: Completed
• Phase: Phase 1
• Start date: February 18, 2014
• Est. completion date: January 11, 2024

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: January 11, 2024
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab
Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.
• Velcade
Administered subcutaneously in accordance with product labeling and local standards.
• Pomalidomide
Administered orally in accordance with product labeling and local standards.
• Dexamethasone
Administered intravenously or orally in accordance with product labeling and local standards.
• Melphalan
Administered orally in accordance with product labeling and local standards.
• Prednisone
Administered intravenously or orally in accordance with product labeling and local standards.
• Thalidomide
Administered orally in accordance with product labeling and local standards.
• Diphenhydramine
Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.
• Acetaminophen
Administered in prophylactic doses by mouth in accordance with product labeling and local standards.
• Carfilzomib
Administered intravenously in accordance with product labeling and local standards.
• Lenalidomide
Administered orally in accordance with product labeling and local standards.
• Montelukast
Administered intravenously or orally only with the first daratumumab dose in accordance with product labeling and local standards.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of participants affected by dose-limiting toxicities		Up to 30 days after the last dose of study medication
Secondary	Maximum observed concentration of daratumumab		Up to post-treatment visit Week 9
Secondary	Number of participants with generation of antibodies to daratumumab		Up to post-treatment visit Week 9
Secondary	Complete response rate		Up to 25 months after last patient receives first dose of study drug
Secondary	Overall response rate		Up to 25 months after last patient receives first dose of study drug
Secondary	Duration of response		Up to 25 months after last patient receives first dose of study drug