Clinical trial NCT02316106: A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma
Official title: A Randomized Phase 2 Trial to Evaluate Three Daratumumab Dose Schedules in Smoldering Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Smoldering multiple myeloma (SMM)
Daratumumab
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-12-12
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate three daratumumab dose schedules in participants with Smoldering Multiple Myeloma.

Detailed description: This is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 3-arm (3 treatment groups), multicenter study of daratumumab in participants diagnosed with intermediate or high-risk Smoldering Multiple Myeloma (SMM \[ie, early disease without any symptoms\]). Participants will be randomized (assigned by chance) to one of 3 treatment groups (arm A \[long intense\], arm B \[intermediate\] and arm C \[short intense\]) to receive daratumumab. Each treatment group will investigate 1 of 3 dosing schedules of daratumumab. The study will include a 28-Day Screening Phase, a Treatment Phase of 1 to 20 treatment cycles (each cycle is 8 weeks in duration for total period of 8 to 160 weeks), and a Follow up Phase of 4-weeks from the last dose of study drug. For participants in Arm A (long intense) and Arm B (intermediate), there is a possibility to extend treatment with IV daratumumab (Q8W) after the end of Cycle 20 if, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade \>=3 treatment related toxicity, and at least stable disease has been achieved. For participants participating in treatment extension, the duration of infusion may be shortened to a 90-minute infusion or can switch to daratumumab 1800mg subcutaneous (Q8w). The Follow-up Phase will continue until death, lost to follow up, consent withdrawal, or study end, whichever occurs first. The end of the study will occur approximately 7 years after the last participant enrolled receives a first dose of study drug. 'Disease assessment will be performed locally per Standard of Care.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of smoldering multiple myeloma (SMM) for less than 5 years
* Have a confirmed diagnosis of intermediate or high-risk SMM, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

* Active multiple myeloma,requiring treatment as defined by the study protocol
* Primary systemic AL (immunoglobulin light chain) amyloidosis
* Prior or concurrent exposure to any of the following: approved or investigational treatments for SMM or/and multiple myeloma, daratumumab or other anti CD-38 therapies, treatment with corticosteroids with a dose greater than (\>) 10 milligram (mg) prednisone per day or equivalent and bone-protecting agents (eg, bisphosphonates, denosumab) or are only allowed if given in a stable dose and for a nonmalignant condition, or received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1
* History of malignancy (other than SMM) within 3 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
* Known chronic obstructive pulmonary disease (COPD) OR moderate or severe persistent asthma within the past 2 years
* Any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) 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

Primary outcomes:
measure: The percentage of participants who achieve a complete response (CR)
timeFrame: Up to 7 years
measure: The percentage of participants that have an event (disease progression or death) per patient-year
timeFrame: Up to 7 years
Secondary outcomes:
measure: The percentage of participants who are minimal residual disease (MRD) negative
timeFrame: Up to 7 years
measure: Time to next treatment (TNT)
timeFrame: Up to 7 years
measure: The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR)
timeFrame: Up to 7 years
measure: The median time of progression free survival (PFS)
timeFrame: Up to 7 years
measure: The percentage of participants with symptomatic multiple myeloma
timeFrame: Up to 7 years
measure: Response to first subsequent multiple myeloma treatment
timeFrame: Up to 7 years
measure: Overall survival rate
timeFrame: Up to 7 years
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Jacksonville
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Seattle
country: United States
state: Washington
city: Box Hill
country: Australia
city: Concord
country: Australia
city: Melbourne
country: Australia
city: Woodville South
country: Australia
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Brno
country: Czechia
city: Hradec Kralove
country: Czechia
city: Praha 2
country: Czechia
city: Lille
country: France
city: Nantes
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Rennes Cedex
country: France
city: Berlin
country: Germany
city: Chemnitz
country: Germany
city: Essen
country: Germany
city: Heidelberg
country: Germany
city: Mainz
country: Germany
city: München
country: Germany
city: Tuebingen
country: Germany
city: Würzburg
country: Germany
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petah Tikva
country: Israel
city: Tel Aviv
country: Israel
city: Amsterdam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Nizhny Novgorod
country: Russian Federation
city: Petrozavodsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: Ankara
country: Turkey
city: Antalya
country: Turkey
city: Izmir
country: Turkey
city: Samsun
country: Turkey
city: Cardiff
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Southampton
country: United Kingdom
city: Surrey
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Chari A, Munder M, Weisel K, Jenner M, Bygrave C, Petrucci MT, Boccadoro M, Cavo M, van de Donk NWCJ, Turgut M, Demirkan F, Karadogan I, Libby E, Kleiman R, Kuppens S, Bandekar R, Neff T, Heuck C, Qi M, Clemens PL, Goldschmidt H. Evaluation of Cardiac Repolarization in the Randomized Phase 2 Study of Intermediate- or High-Risk Smoldering Multiple Myeloma Patients Treated with Daratumumab Monotherapy. Adv Ther. 2021 Feb;38(2):1328-1341. doi: 10.1007/s12325-020-01601-w. Epub 2021 Jan 20.
citation: Landgren CO, Chari A, Cohen YC, Spencer A, Voorhees P, Estell JA, Sandhu I, Jenner MW, Williams C, Cavo M, van de Donk NWCJ, Beksac M, Moreau P, Goldschmidt H, Kuppens S, Bandekar R, Clemens PL, Neff T, Heuck C, Qi M, Hofmeister CC. Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS). Leukemia. 2020 Jul;34(7):1840-1852. doi: 10.1038/s41375-020-0718-z. Epub 2020 Feb 5.