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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Daratumumab; Drug: Velcade; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Acetaminophen; Drug: Melphalan; Drug: Prednisone; Drug: Thalidomide; Drug: Pomalidomide; Drug: Carfilzomib; Drug: Montelukast; Drug: Lenalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lille Cedex, France
  • Nantes, France
  • Paris, France
  • Pessac, France
  • Toulouse cedex 9, France
  • Tours, France
• Spain
  • Badalona, Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Pamplona, Spain
  • Salamanca, Spain
  • Valencia, Spain
• United States
  • California
    • Duarte, California, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • New York
    • New York, New York, United States
    • Rochester, New York, United States
  • North Carolina
    • Charlotte, North Carolina, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
  • Texas
    • Dallas, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daratumumab + VD; Daratumumab will be administered with Velcade-dexamethasone (VD).	Drug: Daratumumab; Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.; Drug: Velcade; Administered subcutaneously in accordance with product labeling and local standards.; Drug: Dexamethasone; Administered intravenously or orally in accordance with product labeling and local standards.; Drug: Diphenhydramine; Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.; Drug: Acetaminophen; Administered in prophylactic doses by mouth in accordance with product labeling and local standards.
Experimental: Daratumumab + VMP; Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).	Drug: Daratumumab; Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.; Drug: Velcade; Administered subcutaneously in accordance with product labeling and local standards.; Drug: Diphenhydramine; Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.; Drug: Acetaminophen; Administered in prophylactic doses by mouth in accordance with product labeling and local standards.; Drug: Melphalan; Administered orally in accordance with product labeling and local standards.; Drug: Prednisone; Administered intravenously or orally in accordance with product labeling and local standards.
Experimental: Daratumumab + VTD; Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).	Drug: Daratumumab; Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.; Drug: Velcade; Administered subcutaneously in accordance with product labeling and local standards.; Drug: Dexamethasone; Administered intravenously or orally in accordance with product labeling and local standards.; Drug: Diphenhydramine; Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.; Drug: Acetaminophen; Administered in prophylactic doses by mouth in accordance with product labeling and local standards.; Drug: Thalidomide; Administered orally in accordance with product labeling and local standards.
Experimental: Daratumumab + Pom-dex; Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).	Drug: Daratumumab; Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.; Drug: Dexamethasone; Administered intravenously or orally in accordance with product labeling and local standards.; Drug: Diphenhydramine; Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.; Drug: Acetaminophen; Administered in prophylactic doses by mouth in accordance with product labeling and local standards.; Drug: Pomalidomide; Administered orally in accordance with product labeling and local standards.
Experimental: Daratumumab + CFZ-dex; Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.	Drug: Daratumumab; Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.; Drug: Dexamethasone; Administered intravenously or orally in accordance with product labeling and local standards.; Drug: Diphenhydramine; Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.; Drug: Acetaminophen; Administered in prophylactic doses by mouth in accordance with product labeling and local standards.; Drug: Carfilzomib; Administered intravenously in accordance with product labeling and local standards.; Drug: Montelukast; Administered intravenously or orally only with the first daratumumab dose in accordance with product labeling and local standards.
Experimental: Daratumumab + KRd; Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.	Drug: Daratumumab; Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.; Drug: Dexamethasone; Administered intravenously or orally in accordance with product labeling and local standards.; Drug: Diphenhydramine; Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.; Drug: Acetaminophen; Administered in prophylactic doses by mouth in accordance with product labeling and local standards.; Drug: Carfilzomib; Administered intravenously in accordance with product labeling and local standards.; Drug: Montelukast; Administered intravenously or orally only with the first daratumumab dose in accordance with product labeling and local standards.; Drug: Lenalidomide; Administered orally in accordance with product labeling and local standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Number of participants affected by dose-limiting toxicities	Up to 30 days after the last dose of study medication

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration of daratumumab	Up to post-treatment visit Week 9
Number of participants with generation of antibodies to 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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Leleu X, Beksac M, Chou T, Dimopoulos M, Yoon SS, Prince HM, Pour L, Shelekhova T, Chari A, Khurana M, Zhang J, Obreja M, Qi M, Oriol A, Siegel D. Efficacy and safety of weekly carfilzomib (70 mg/m2), dexamethasone, and daratumumab (KdD70) is comparable to twice-weekly KdD56 while being a more convenient dosing option: a cross-study comparison of the CANDOR and EQUULEUS studies. Leuk Lymphoma. 2021 Feb;62(2):358-367. doi: 10.1080/10428194.2020.1832672. Epub 2020 Oct 28.
• Xu XS, Moreau P, Usmani SZ, Lonial S, Jakubowiak A, Oriol A, Krishnan A, Blade J, Luo M, Sun YN, Zhou H, Nnane I, Deraedt W, Qi M, Ukropec J, Clemens PL. Split First Dose Administration of Intravenous Daratumumab for the Treatment of Multiple Myeloma (MM): Clinical and Population Pharmacokinetic Analyses. Adv Ther. 2020 Apr;37(4):1464-1478. doi: 10.1007/s12325-020-01247-8. Epub 2020 Feb 20.
• Chari A, Martinez-Lopez J, Mateos MV, Blade J, Benboubker L, Oriol A, Arnulf B, Rodriguez-Otero P, Pineiro L, Jakubowiak A, de Boer C, Wang J, Clemens PL, Ukropec J, Schecter J, Lonial S, Moreau P. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood. 2019 Aug 1;134(5):421-431. doi: 10.1182/blood.2019000722. Epub 2019 May 21.
• Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, Weiss BM, Krishnan A, Lentzsch S, Comenzo R, Wang J, Nottage K, Chiu C, Khokhar NZ, Ahmadi T, Lonial S. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017 Aug 24;130(8):974-981. doi: 10.1182/blood-2017-05-785246. Epub 2017 Jun 21.
• He J, Berringer H, Heeg B, Ruan H, Kampfenkel T, Dwarakanathan HR, Johnston S, Mendes J, Lam A, Bathija S, Mackay EK. Indirect Treatment Comparison of Daratumumab, Pomalidomide, and Dexamethasone Versus Standard of Care in Patients with Difficult-to-Treat Relapsed/Refractory Multiple Myeloma. Adv Ther. 2022 Sep;39(9):4230-4249. doi: 10.1007/s12325-022-02226-x. Epub 2022 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2014
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 11, 2024

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: November 25, 2013
• First Posted (Estimated): December 3, 2013

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Multiple myeloma; Daratumumab; JNJ-54767414; Velcade-dexamethasone; Velcade-melphalan-prednisone; Velcade-thalidomide-dexamethasone; Pomalidomide-dexamethasone; Carfilzomib-dexamethasone; Carfilzomib-lenalidomide-dexamethasone; Anti-CD38 Monoclonal Antibody; Immunomodulatory drug; IMiD
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Sleep Aids, Pharmaceutical; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Hypnotics and Sedatives; Hormone Antagonists; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Respiratory System Agents; Anti-Asthmatic Agents; Anti-Allergic Agents; Antipruritics; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Histamine H1 Antagonists; Cytochrome P-450 CYP1A2 Inducers; Leukotriene Antagonists; Lenalidomide; Bortezomib; Dexamethasone; Acetaminophen; Prednisone; Melphalan; Pomalidomide; Daratumumab; Thalidomide; Diphenhydramine; Promethazine; Montelukast
• Other Study ID Numbers: CR103015; 54767414MMY1001 (Other Identifier: Janssen Research & Development, LLC); 2013-003491-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No