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A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
daratumumab
daratumumab
daratumumab
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 Smoldering multiple myeloma (SMM), Daratumumab

Eligibility Criteria

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

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A (Long Intense)

Arm B (Intermediate)

Arm C (Short Intense)

Arm Description

Outcomes

Primary Outcome Measures

The percentage of participants who achieve a complete response (CR)
CR, defined having negative immunofixation on the serum and urine, and <5% plasma cells (PCs) in bone marrow.
The percentage of participants that have an event (disease progression or death) per patient-year

Secondary Outcome Measures

The percentage of participants who are minimal residual disease (MRD) negative
Time to next treatment (TNT)
TNT, defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment.
The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR)
See definition of CR above. PR, defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours.
The median time of progression free survival (PFS)
PFS is defined as time from date of randomization to date of initial documented disease progression (PD) according to SLiM-CRAB (S=sixty, Li=light chains, M=MRI, C=calcium [elevated], R=renal failure, A=anemia, B=bone lesions) criteria, myeloma defining events, or date of death, whichever occurs first. As per SLiM-CRAB criteria, clonal bone marrow plasma cell percentage >=60%, Involved : uninvolved serum free Li ratio >= 100, >1 focal lesion on MRI studies, calcium elevation: >0.25 millimole per liter (mmol/L) ( >1 milligram per deciliter [mg/dL]) higher than upper limit of normal or >2.75 mmol/L (>11 mg/dL); creatinine clearance <40 milliliter per minute (mL/min) or serum creatinine >177 micromole per liter (µmol/L) (>2 mg/dL); hemoglobin <10 gram per deciliter (g/dL) (<6.5 mmol/L) or >2 g/dL (>1.25 mmol/L) lower than lower limit of normal; 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT).
The percentage of participants with symptomatic multiple myeloma
Response to first subsequent multiple myeloma treatment
Overall survival rate

Full Information

First Posted
December 10, 2014
Last Updated
October 10, 2023
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02316106
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 20, 2015 (Actual)
Primary Completion Date
June 2, 2023 (Actual)
Study Completion Date
June 3, 2024 (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 Drug Product
Yes
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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Smoldering multiple myeloma (SMM), Daratumumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (Long Intense)
Arm Type
Experimental
Arm Title
Arm B (Intermediate)
Arm Type
Experimental
Arm Title
Arm C (Short Intense)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
daratumumab
Intervention Description
16 mg/kg administered by intravenous (IV) infusion once every week in Cycle 1, every other week in Cycle 2 and Cycle 3, every 4 weeks in Cycle 4 to Cycle 7, and from Cycle 8 to Cycle 20 on Day 1 of each cycle. If, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade greater than or equal to (>=) 3 treatment related toxicity, and at least stable disease has been achieved, treatment can be extended and given every 8 weeks after Cycle 20. 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).
Intervention Type
Drug
Intervention Name(s)
daratumumab
Intervention Description
16 mg/kg administered by IV infusion once every week in Cycle 1, and then on Day 1 of each cycle from Cycle 2 to Cycle 20, and every 8 weeks after Cycle 20. If, as per investigator discretion, there is a positive benefit/risk ratio, absence of Grade greater than or equal to (>=) 3 treatment related toxicity, and at least stable disease has been achieved, treatment can be extended and given every 8 weeks after Cycle 20. 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).
Intervention Type
Drug
Intervention Name(s)
daratumumab
Intervention Description
16 mg/kg administered by IV infusion once every week in Cycle 1 only. Treatment cycles are 8 weeks in length.
Primary Outcome Measure Information:
Title
The percentage of participants who achieve a complete response (CR)
Description
CR, defined having negative immunofixation on the serum and urine, and <5% plasma cells (PCs) in bone marrow.
Time Frame
Up to 7 years
Title
The percentage of participants that have an event (disease progression or death) per patient-year
Time Frame
Up to 7 years
Secondary Outcome Measure Information:
Title
The percentage of participants who are minimal residual disease (MRD) negative
Time Frame
Up to 7 years
Title
Time to next treatment (TNT)
Description
TNT, defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment.
Time Frame
Up to 7 years
Title
The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR)
Description
See definition of CR above. PR, defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours.
Time Frame
Up to 7 years
Title
The median time of progression free survival (PFS)
Description
PFS is defined as time from date of randomization to date of initial documented disease progression (PD) according to SLiM-CRAB (S=sixty, Li=light chains, M=MRI, C=calcium [elevated], R=renal failure, A=anemia, B=bone lesions) criteria, myeloma defining events, or date of death, whichever occurs first. As per SLiM-CRAB criteria, clonal bone marrow plasma cell percentage >=60%, Involved : uninvolved serum free Li ratio >= 100, >1 focal lesion on MRI studies, calcium elevation: >0.25 millimole per liter (mmol/L) ( >1 milligram per deciliter [mg/dL]) higher than upper limit of normal or >2.75 mmol/L (>11 mg/dL); creatinine clearance <40 milliliter per minute (mL/min) or serum creatinine >177 micromole per liter (µmol/L) (>2 mg/dL); hemoglobin <10 gram per deciliter (g/dL) (<6.5 mmol/L) or >2 g/dL (>1.25 mmol/L) lower than lower limit of normal; 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT).
Time Frame
Up to 7 years
Title
The percentage of participants with symptomatic multiple myeloma
Time Frame
Up to 7 years
Title
Response to first subsequent multiple myeloma treatment
Time Frame
Up to 7 years
Title
Overall survival rate
Time Frame
Up to 7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
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
Little Rock
State/Province
Arkansas
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
West Palm Beach
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
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Boston
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Hackensack
State/Province
New Jersey
Country
United States
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New York
State/Province
New York
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
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Columbus
State/Province
Ohio
Country
United States
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Philadelphia
State/Province
Pennsylvania
Country
United States
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Nashville
State/Province
Tennessee
Country
United States
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Seattle
State/Province
Washington
Country
United States
City
Box Hill
Country
Australia
City
Concord
Country
Australia
City
Melbourne
Country
Australia
City
Woodville South
Country
Australia
City
Calgary
State/Province
Alberta
Country
Canada
City
Edmonton
State/Province
Alberta
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
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
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München
Country
Germany
City
Tuebingen
Country
Germany
City
Würzburg
Country
Germany
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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

12. IPD Sharing Statement

Citations:
PubMed Identifier
33474705
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.
Results Reference
derived
PubMed Identifier
32024950
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.
Results Reference
derived

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A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma

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