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

NCT01998971 | Completed Phase 1 DMC

• 3 other identifiers: CR10301554767414MMY10012013-003491-12
• Study Type: interventional
• Target: 240
• Locations: 3 countries
• Sites: 22

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.

Conditions

Multiple Myeloma

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (6)

Daratumumab + VD

EXPERIMENTAL

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

Drug: Daratumumab; Drug: Velcade; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Acetaminophen

Daratumumab + VMP

EXPERIMENTAL

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

Drug: Daratumumab; Drug: Velcade; Drug: Melphalan; Drug: Prednisone; Drug: Diphenhydramine; Drug: Acetaminophen

Daratumumab + VTD

EXPERIMENTAL

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

Drug: Daratumumab; Drug: Velcade; Drug: Dexamethasone; Drug: Thalidomide; Drug: Diphenhydramine; Drug: Acetaminophen

Daratumumab + Pom-dex

EXPERIMENTAL

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

Drug: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Acetaminophen

Daratumumab + CFZ-dex

EXPERIMENTAL

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

Drug: Daratumumab; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Acetaminophen; Drug: Carfilzomib; Drug: Montelukast

Daratumumab + KRd

EXPERIMENTAL

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

Drug: Daratumumab; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Acetaminophen; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Montelukast

Interventions

Daratumumab DRUG

Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.

Daratumumab + CFZ-dex; Daratumumab + KRd; Daratumumab + Pom-dex; Daratumumab + VD; Daratumumab + VMP; Daratumumab + VTD

Velcade DRUG

Administered subcutaneously in accordance with product labeling and local standards.

Daratumumab + VD; Daratumumab + VMP; Daratumumab + VTD

Pomalidomide DRUG

Administered orally in accordance with product labeling and local standards.

Daratumumab + Pom-dex

Dexamethasone DRUG

Administered intravenously or orally in accordance with product labeling and local standards.

Daratumumab + CFZ-dex; Daratumumab + KRd; Daratumumab + Pom-dex; Daratumumab + VD; Daratumumab + VTD

Melphalan DRUG

Administered orally in accordance with product labeling and local standards.

Daratumumab + VMP

Prednisone DRUG

Administered intravenously or orally in accordance with product labeling and local standards.

Daratumumab + VMP

Thalidomide DRUG

Administered orally in accordance with product labeling and local standards.

Daratumumab + VTD

Diphenhydramine DRUG

Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.

Daratumumab + CFZ-dex; Daratumumab + KRd; Daratumumab + Pom-dex; Daratumumab + VD; Daratumumab + VMP; Daratumumab + VTD

Acetaminophen DRUG

Administered in prophylactic doses by mouth in accordance with product labeling and local standards.

Daratumumab + CFZ-dex; Daratumumab + KRd; Daratumumab + Pom-dex; Daratumumab + VD; Daratumumab + VMP; Daratumumab + VTD

Carfilzomib DRUG

Administered intravenously in accordance with product labeling and local standards.

Daratumumab + CFZ-dex; Daratumumab + KRd

Lenalidomide DRUG

Administered orally in accordance with product labeling and local standards.

Daratumumab + KRd

Montelukast DRUG

Administered intravenously or orally only with the first daratumumab dose in accordance with product labeling and local standards.

Daratumumab + CFZ-dex; Daratumumab + KRd

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (22)

Unknown Facility

Duarte, California, United States

Location

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Boston, Massachusetts, United States

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New York, New York, United States

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Rochester, New York, United States

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Charlotte, North Carolina, United States

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Philadelphia, Pennsylvania, United States

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Dallas, Texas, United States

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Lille, France

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Nantes, France

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Paris, France

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Pessac, France

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Toulouse, France

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Tours, France

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Badalona, Spain

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Barcelona, Spain

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Madrid, Spain

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Pamplona, Spain

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Salamanca, Spain

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Valencia, Spain

Location

Related Publications (6)

• Moreau P, Chari A, Oriol A, Martinez-Lopez J, Haenel M, Touzeau C, Ailawadhi S, Besemer B, de la Rubia Comos J, Encinas C, Mateos MV, Salwender H, Rodriguez-Otero P, Hulin C, Karlin L, Sureda Balari A, Bargay J, Benboubker L, Rosinol L, Tarantolo S, Terebelo H, Yang S, Wang J, Nnane I, Qi M, Kosh M, Delioukina M, Goldschmidt H. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. Blood Cancer J. 2023 Mar 7;13(1):33. doi: 10.1038/s41408-023-00805-x. No abstract available.

  PMID: 36882409 DERIVED

• 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.

  PMID: 35876974 DERIVED

• 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.

  PMID: 33112184 DERIVED

• 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.

  PMID: 32078124 DERIVED

• 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.

  PMID: 31113777 DERIVED

• 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.

  PMID: 28637662 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; pomalidomide; Dexamethasone; Melphalan; Prednisone; Thalidomide; Diphenhydramine; Acetaminophen; carfilzomib; Lenalidomide; montelukast

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Acetanilides; Anilides; Amides; Aniline Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2013
• First Posted: December 3, 2013
• Study Start: February 18, 2014
• Primary Completion: January 31, 2019
• Study Completion: January 11, 2024
• Last Updated: April 25, 2025

Record last verified: 2025-04

Locations

ES (6); FR (6); US (10)