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

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Daratumumab
Velcade
Pomalidomide
Dexamethasone
Melphalan
Prednisone
Thalidomide
Diphenhydramine
Acetaminophen
Carfilzomib
Lenalidomide
Montelukast
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Daratumumab + VD

Daratumumab + VMP

Daratumumab + VTD

Daratumumab + Pom-dex

Daratumumab + CFZ-dex

Daratumumab + KRd

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
Number of participants affected by dose-limiting toxicities

Secondary Outcome Measures

Maximum observed concentration of daratumumab
Number of participants with generation of antibodies to daratumumab
Complete response rate
Overall response rate
Duration of response

Full Information

First Posted
November 25, 2013
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01998971
Brief Title
A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 18, 2014 (Actual)
Primary Completion Date
January 31, 2019 (Actual)
Study Completion Date
December 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
242 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Daratumumab + VD
Arm Type
Experimental
Arm Description
Daratumumab will be administered with Velcade-dexamethasone (VD).
Arm Title
Daratumumab + VMP
Arm Type
Experimental
Arm Description
Daratumumab will be administered with Velcade-melphalan-prednisone (VMP).
Arm Title
Daratumumab + VTD
Arm Type
Experimental
Arm Description
Daratumumab will be administered with Velcade-thalidomide-dexamethasone (VTD).
Arm Title
Daratumumab + Pom-dex
Arm Type
Experimental
Arm Description
Daratumumab will be administered with pomalidomide-dexamethasone (Pom-dex).
Arm Title
Daratumumab + CFZ-dex
Arm Type
Experimental
Arm Description
Daratumumab will be administered with carfilzomib (CFZ)-dexamethasone (CFZ-dex) regimen.
Arm Title
Daratumumab + KRd
Arm Type
Experimental
Arm Description
Daratumumab will be administered with carfilzomib- lenalidomide-dexamethasone (KRd) regimen.
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Intervention Description
Administered by either intravenous or subcutaneous infusions, in combination with the applicable backbone treatment.
Intervention Type
Drug
Intervention Name(s)
Velcade
Intervention Description
Administered subcutaneously in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Intervention Description
Administered orally in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Administered intravenously or orally in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Administered orally in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Administered intravenously or orally in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Intervention Description
Administered orally in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Diphenhydramine
Intervention Description
Administered in prophylactic doses intravenously (or equivalent) in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Description
Administered in prophylactic doses by mouth in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Intervention Description
Administered intravenously in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Administered orally in accordance with product labeling and local standards.
Intervention Type
Drug
Intervention Name(s)
Montelukast
Intervention Description
Administered intravenously or orally only with the first daratumumab dose in accordance with product labeling and local standards.
Primary Outcome Measure Information:
Title
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
Title
Number of participants affected by dose-limiting toxicities
Time Frame
Up to 30 days after the last dose of study medication
Secondary Outcome Measure Information:
Title
Maximum observed concentration of daratumumab
Time Frame
Up to post-treatment visit Week 9
Title
Number of participants with generation of antibodies to daratumumab
Time Frame
Up to post-treatment visit Week 9
Title
Complete response rate
Time Frame
Up to 25 months after last patient receives first dose of study drug
Title
Overall response rate
Time Frame
Up to 25 months after last patient receives first dose of study drug
Title
Duration of response
Time Frame
Up to 25 months after last patient receives first dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Duarte
State/Province
California
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
New York
State/Province
New York
Country
United States
City
Rochester
State/Province
New York
Country
United States
City
Charlotte
State/Province
North Carolina
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
Lille Cedex
Country
France
City
Nantes
Country
France
City
Paris
Country
France
City
Pessac
Country
France
City
Toulouse cedex 9
Country
France
City
Tours
Country
France
City
Badalona
Country
Spain
City
Barcelona
Country
Spain
City
Madrid
Country
Spain
City
Pamplona
Country
Spain
City
Salamanca
Country
Spain
City
Valencia
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
35876974
Citation
He J, Berringer H, Heeg B, Ruan H, Kampfenkel T, Dwarakanathan HR, Johnston S, Mendes J, Lam A, Bathija S, Mackay E. 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.
Results Reference
derived
PubMed Identifier
33112184
Citation
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.
Results Reference
derived
PubMed Identifier
32078124
Citation
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.
Results Reference
derived
PubMed Identifier
31113777
Citation
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.
Results Reference
derived
PubMed Identifier
28637662
Citation
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.
Results Reference
derived

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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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