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

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ClinicalTrials.gov Identifier: NCT01998971

Recruitment Status : Active, not recruiting

First Posted : December 3, 2013

Last Update Posted : September 10, 2021

Sponsor:

Information provided by (Responsible Party):

Janssen Research & Development, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Daratumumab Drug: Velcade Drug: Pomalidomide Drug: Dexamethasone Drug: Melphalan Drug: Prednisone Drug: Thalidomide Drug: Diphenhydramine Drug: Acetaminophen Drug: Carfilzomib Drug: Lenalidomide Drug: Montelukast	Phase 1

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 subjects per VTD and VMP backbone treatment regimen, 6 for the VD regimen, up to 100 subjects in the Pom-dex regimen, 80 for the CFZ-dex regimen [10 subjects will receive a single-dose of daratumumab and the remaining subjects 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 until disease progression (in the Pom-dex and CFZ-dex regimen). Follow-up will continue until the study ends (approximately 15 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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	242 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	February 18, 2014
Actual Primary Completion Date :	January 31, 2019
Estimated Study Completion Date :	July 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Multiple myeloma

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Daratumumab

Genetic and Rare Diseases Information Center resources: Multiple Myeloma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Daratumumab + VD Daratumumab will be administered with Velcade-dexamethasone (VD).	Drug: Daratumumab Administered by intravenous infusion 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 intravenous infusion in combination with the applicable backbone treatment. Drug: Velcade Administered subcutaneously 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. 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 + VTD Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).	Drug: Daratumumab Administered by intravenous infusion 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: Thalidomide Administered 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 + Pom-dex Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).	Drug: Daratumumab Administered by intravenous infusion in combination with the applicable backbone treatment. Drug: Pomalidomide Administered orally 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 + CFZ-dex Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.	Drug: Daratumumab Administered by intravenous infusion 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 intravenous infusion 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: Lenalidomide Administered orally 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.

Outcome Measures

Primary Outcome Measures :

Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) [ Time Frame: Up to 30 days after the last dose of study medication ]
Number of participants affected by dose-limiting toxicities [ Time Frame: Up to 30 days after the last dose of study medication ]

Secondary Outcome Measures :

Maximum observed concentration of daratumumab [ Time Frame: Up to post-treatment visit Week 9 ]
Number of participants with generation of antibodies to daratumumab [ Time Frame: Up to post-treatment visit Week 9 ]
Complete response rate [ Time Frame: Up to 15 months after last patient receives first dose of study drug ]
Overall response rate [ Time Frame: Up to 15 months after last patient receives first dose of study drug ]
Duration of response [ Time Frame: Up to 15 months after last patient receives first dose of study drug ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01998971

Locations

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United States, California

Duarte, California, United States
United States, Georgia

Atlanta, Georgia, United States
United States, Illinois

Chicago, Illinois, United States
United States, Indiana

Indianapolis, Indiana, United States
United States, Massachusetts

Boston, Massachusetts, United States
United States, New York

New York, New York, United States

Rochester, New York, United States
United States, North Carolina

Charlotte, North Carolina, United States
United States, Pennsylvania

Philadelphia, Pennsylvania, United States
United States, Texas

Dallas, Texas, United States
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

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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Study Director:	Janssen Research & Development, LLC Clinical Trial	Janssen Research & Development, LLC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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/m(2)), 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, Bladé 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, Bladé 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.

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Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01998971
Other Study ID Numbers:	CR103015 54767414MMY1001 ( Other Identifier: Janssen Research & Development, LLC ) 2013-003491-12 ( EudraCT Number )
First Posted:	December 3, 2013 Key Record Dates
Last Update Posted:	September 10, 2021
Last Verified:	September 2021

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Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Janssen Research & Development, LLC:


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:

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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Acetaminophen	Diphenhydramine Promethazine Thalidomide Dexamethasone Prednisone Lenalidomide Melphalan Bortezomib Pomalidomide Daratumumab Montelukast Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents

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