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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02316106

Collaborator

(none)

123

Enrollment

Locations

Arms

98.6

Anticipated Duration (Months)

2.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: daratumumab Drug: daratumumab Drug: daratumumab	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

123 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase 2 Trial to Evaluate Three Daratumumab Dose Schedules in Smoldering Multiple Myeloma

Actual Study Start Date :

May 20, 2015

Anticipated Primary Completion Date :

Aug 8, 2023

Anticipated Study Completion Date :

Aug 8, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (Long Intense)	Drug: 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).
Experimental: Arm B (Intermediate)	Drug: 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).
Experimental: Arm C (Short Intense)	Drug: daratumumab 16 mg/kg administered by IV infusion once every week in Cycle 1 only. Treatment cycles are 8 weeks in length.

Arm

Intervention/Treatment

Experimental: Arm A (Long Intense)

Drug: 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).

Experimental: Arm B (Intermediate)

Drug: 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).

Experimental: Arm C (Short Intense)

Drug: daratumumab

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

Outcome Measures

Primary Outcome Measures

The percentage of participants who achieve a complete response (CR) [Up to 7 years]
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 [Up to 7 years]

Secondary Outcome Measures

The percentage of participants who are minimal residual disease (MRD) negative [Up to 7 years]
Time to next treatment (TNT) [Up to 7 years]
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) [Up to 7 years]
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) [Up to 7 years]
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 [Up to 7 years]
Response to first subsequent multiple myeloma treatment [Up to 7 years]
Overall survival rate [Up to 7 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	City	State	Country
1	Little Rock	Arkansas	United States
2	Jacksonville	Florida	United States
3	West Palm Beach	Florida	United States
4	Atlanta	Georgia	United States
5	Boston	Massachusetts	United States
6	Ann Arbor	Michigan	United States
7	Saint Louis	Missouri	United States
8	Hackensack	New Jersey	United States
9	New York	New York	United States
10	Chapel Hill	North Carolina	United States
11	Cincinnati	Ohio	United States
12	Columbus	Ohio	United States
13	Philadelphia	Pennsylvania	United States
14	Nashville	Tennessee	United States
15	Seattle	Washington	United States
16	Box Hill		Australia
17	Concord		Australia
18	Melbourne		Australia
19	Woodville South		Australia
20	Calgary	Alberta	Canada
21	Edmonton	Alberta	Canada
22	Toronto	Ontario	Canada
23	Brno		Czechia
24	Hradec Kralove		Czechia
25	Praha 2		Czechia
26	Lille		France
27	Nantes		France
28	Paris		France
29	Pierre Benite		France
30	Rennes Cedex		France
31	Berlin		Germany
32	Chemnitz		Germany
33	Essen		Germany
34	Heidelberg		Germany
35	Mainz		Germany
36	München		Germany
37	Tuebingen		Germany
38	Würzburg		Germany
39	Haifa		Israel
40	Jerusalem		Israel
41	Petah Tikva		Israel
42	Tel Aviv		Israel
43	Amsterdam		Netherlands
44	Rotterdam		Netherlands
45	Utrecht		Netherlands
46	Nizhny Novgorod		Russian Federation
47	Petrozavodsk		Russian Federation
48	Ryazan		Russian Federation
49	St-Petersburg		Russian Federation
50	Ankara		Turkey
51	Antalya		Turkey
52	Izmir		Turkey
53	Samsun		Turkey
54	Cardiff		United Kingdom
55	Nottingham		United Kingdom
56	Southampton		United Kingdom
57	Surrey		United Kingdom