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

NCT ID: NCT01998971

Last Updated: 2025-04-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-18

Study Completion Date

2024-01-11

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Daratumumab + VD

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

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

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

Velcade

Intervention Type DRUG

Administered subcutaneously in accordance with product labeling and local standards.

Dexamethasone

Intervention Type DRUG

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

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Daratumumab + VMP

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

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

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

Velcade

Intervention Type DRUG

Administered subcutaneously in accordance with product labeling and local standards.

Melphalan

Intervention Type DRUG

Administered orally in accordance with product labeling and local standards.

Prednisone

Intervention Type DRUG

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

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Daratumumab + VTD

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

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

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

Velcade

Intervention Type DRUG

Administered subcutaneously in accordance with product labeling and local standards.

Dexamethasone

Intervention Type DRUG

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

Thalidomide

Intervention Type DRUG

Administered orally in accordance with product labeling and local standards.

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Daratumumab + Pom-dex

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

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

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

Pomalidomide

Intervention Type DRUG

Administered orally in accordance with product labeling and local standards.

Dexamethasone

Intervention Type DRUG

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

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Daratumumab + CFZ-dex

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

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

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

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Carfilzomib

Intervention Type DRUG

Administered intravenously in accordance with product labeling and local standards.

Montelukast

Intervention Type DRUG

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

Daratumumab + KRd

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

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

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

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Carfilzomib

Intervention Type DRUG

Administered intravenously in accordance with product labeling and local standards.

Lenalidomide

Intervention Type DRUG

Administered orally in accordance with product labeling and local standards.

Montelukast

Intervention Type DRUG

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

Interventions

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Daratumumab

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

Intervention Type DRUG

Velcade

Administered subcutaneously in accordance with product labeling and local standards.

Intervention Type DRUG

Pomalidomide

Administered orally in accordance with product labeling and local standards.

Intervention Type DRUG

Dexamethasone

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

Intervention Type DRUG

Melphalan

Administered orally in accordance with product labeling and local standards.

Intervention Type DRUG

Prednisone

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

Intervention Type DRUG

Thalidomide

Administered orally in accordance with product labeling and local standards.

Intervention Type DRUG

Diphenhydramine

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

Intervention Type DRUG

Acetaminophen

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

Intervention Type DRUG

Carfilzomib

Administered intravenously in accordance with product labeling and local standards.

Intervention Type DRUG

Lenalidomide

Administered orally in accordance with product labeling and local standards.

Intervention Type DRUG

Montelukast

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Duarte, California, United States

Site Status

Atlanta, Georgia, United States

Site Status

Chicago, Illinois, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Boston, Massachusetts, United States

Site Status

New York, New York, United States

Site Status

Rochester, New York, United States

Site Status

Charlotte, North Carolina, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Dallas, Texas, United States

Site Status

Lille, , France

Site Status

Nantes, , France

Site Status

Paris, , France

Site Status

Pessac, , France

Site Status

Toulouse, , France

Site Status

Tours, , France

Site Status

Badalona, , Spain

Site Status

Barcelona, , Spain

Site Status

Madrid, , Spain

Site Status

Pamplona, , Spain

Site Status

Salamanca, , Spain

Site Status

Valencia, , Spain

Site Status

Countries

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United States France Spain

References

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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.

Reference Type DERIVED
PMID: 32078124 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31113777 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28637662 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36882409 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35876974 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33112184 (View on PubMed)

Other Identifiers

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54767414MMY1001

Identifier Type: OTHER

Identifier Source: secondary_id

2013-003491-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR103015

Identifier Type: -

Identifier Source: org_study_id

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