Clinical trial NCT01998971: 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
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-12-03
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)
timeFrame: Up to 30 days after the last dose of study medication
measure: Number of participants affected by dose-limiting toxicities
timeFrame: Up to 30 days after the last dose of study medication
Secondary outcomes:
measure: Maximum observed concentration of daratumumab
timeFrame: Up to post-treatment visit Week 9
measure: Number of participants with generation of antibodies to daratumumab
timeFrame: Up to post-treatment visit Week 9
measure: Complete response rate
timeFrame: Up to 25 months after last patient receives first dose of study drug
measure: Overall response rate
timeFrame: Up to 25 months after last patient receives first dose of study drug
measure: Duration of response
timeFrame: Up to 25 months after last patient receives first dose of study drug
Other outcomes:
Locations:
city: Duarte
country: United States
state: California
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
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
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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.
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.