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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02316106




Registration number
NCT02316106
Ethics application status
Date submitted
10/12/2014
Date registered
12/12/2014
Date last updated
10/09/2021

Titles & IDs
Public title
A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma
Scientific title
A Randomized Phase 2 Trial to Evaluate Three Daratumumab Dose Schedules in Smoldering Multiple Myeloma
Secondary ID [1] 0 0
54767414SMM2001
Secondary ID [2] 0 0
CR106449
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - daratumumab
Treatment: Drugs - daratumumab
Treatment: Drugs - daratumumab

Experimental: Arm A (Long Intense) -

Experimental: Arm B (Intermediate) -

Experimental: Arm C (Short Intense) -


Treatment: Drugs: daratumumab
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).

Treatment: Drugs: daratumumab
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).

Treatment: Drugs: daratumumab
16 mg/kg administered by IV infusion once every week in Cycle 1 only. Treatment cycles are 8 weeks in length.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 7 years
Primary outcome [2] 0 0
The percentage of participants that have an event (disease progression or death) per patient-year
Timepoint [2] 0 0
Up to 7 years
Secondary outcome [1] 0 0
The percentage of participants who are minimal residual disease (MRD) negative
Timepoint [1] 0 0
Up to 7 years
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 7 years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Up to 7 years
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Up to 7 years
Secondary outcome [5] 0 0
The percentage of participants with symptomatic multiple myeloma
Timepoint [5] 0 0
Up to 7 years
Secondary outcome [6] 0 0
Response to first subsequent multiple myeloma treatment
Timepoint [6] 0 0
Up to 7 years
Secondary outcome [7] 0 0
Overall survival rate
Timepoint [7] 0 0
Up to 7 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Box Hill
Recruitment hospital [2] 0 0
- Concord
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Woodville South
Recruitment postcode(s) [1] 0 0
- Box Hill
Recruitment postcode(s) [2] 0 0
- Concord
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Czechia
State/province [16] 0 0
Brno
Country [17] 0 0
Czechia
State/province [17] 0 0
Hradec Kralove
Country [18] 0 0
Czechia
State/province [18] 0 0
Praha 2
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Nantes
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Pierre Benite
Country [23] 0 0
France
State/province [23] 0 0
Rennes Cedex
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Germany
State/province [25] 0 0
Chemnitz
Country [26] 0 0
Germany
State/province [26] 0 0
Essen
Country [27] 0 0
Germany
State/province [27] 0 0
Heidelberg
Country [28] 0 0
Germany
State/province [28] 0 0
Mainz
Country [29] 0 0
Germany
State/province [29] 0 0
München
Country [30] 0 0
Germany
State/province [30] 0 0
Tuebingen
Country [31] 0 0
Germany
State/province [31] 0 0
Würzburg
Country [32] 0 0
Israel
State/province [32] 0 0
Haifa
Country [33] 0 0
Israel
State/province [33] 0 0
Jerusalem
Country [34] 0 0
Israel
State/province [34] 0 0
Petah Tikva
Country [35] 0 0
Israel
State/province [35] 0 0
Tel Aviv
Country [36] 0 0
Netherlands
State/province [36] 0 0
Amsterdam
Country [37] 0 0
Netherlands
State/province [37] 0 0
Rotterdam
Country [38] 0 0
Netherlands
State/province [38] 0 0
Utrecht
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Nizhny Novgorod
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Petrozavodsk
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Ryazan
Country [42] 0 0
Russian Federation
State/province [42] 0 0
St-Petersburg
Country [43] 0 0
Turkey
State/province [43] 0 0
Ankara
Country [44] 0 0
Turkey
State/province [44] 0 0
Antalya
Country [45] 0 0
Turkey
State/province [45] 0 0
Izmir
Country [46] 0 0
Turkey
State/province [46] 0 0
Samsun
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Cardiff
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Nottingham
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Southampton
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate three daratumumab dose schedules in participants
with Smoldering Multiple Myeloma.
Trial website
https://clinicaltrials.gov/show/NCT02316106
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications