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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01998971
Collaborator
(none)
242
Enrollment
22
Locations
6
Arms
100.4
Anticipated Duration (Months)
11
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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 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

Study Type:
Interventional
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 :
Feb 18, 2014
Actual Primary Completion Date :
Jan 31, 2019
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

ArmIntervention/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

  1. 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]

  2. Number of participants affected by dose-limiting toxicities [Up to 30 days after the last dose of study medication]

Secondary Outcome Measures

  1. Maximum observed concentration of daratumumab [Up to post-treatment visit Week 9]

  2. Number of participants with generation of antibodies to daratumumab [Up to post-treatment visit Week 9]

  3. Complete response rate [Up to 15 months after last patient receives first dose of study drug]

  4. Overall response rate [Up to 15 months after last patient receives first dose of study drug]

  5. Duration of response [Up to 15 months after last patient receives first dose of study drug]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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, Waldenstr√∂m'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

Locations

SiteCityStateCountryPostal Code
1DuarteCaliforniaUnited States
2AtlantaGeorgiaUnited States
3ChicagoIllinoisUnited States
4IndianapolisIndianaUnited States
5BostonMassachusettsUnited States
6New YorkNew YorkUnited States
7RochesterNew YorkUnited States
8CharlotteNorth CarolinaUnited States
9PhiladelphiaPennsylvaniaUnited States
10DallasTexasUnited States
11Lille CedexFrance
12NantesFrance
13ParisFrance
14PessacFrance
15Toulouse cedex 9France
16ToursFrance
17BadalonaSpain
18BarcelonaSpain
19MadridSpain
20PamplonaSpain
21SalamancaSpain
22ValenciaSpain

Sponsors and Collaborators

  • Janssen Research & Development, LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01998971
Other Study ID Numbers:
  • CR103015
  • 54767414MMY1001
  • 2013-003491-12
First Posted:
Dec 3, 2013
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021

Study Results

No Results Posted as of Oct 8, 2021