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
57
Locations
3
Arms
98.6
Anticipated Duration (Months)
2.2
Patients Per Site
0
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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

  1. 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.

  2. The percentage of participants that have an event (disease progression or death) per patient-year [Up to 7 years]

Secondary Outcome Measures

  1. The percentage of participants who are minimal residual disease (MRD) negative [Up to 7 years]

  2. 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.

  3. 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.

  4. 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).

  5. The percentage of participants with symptomatic multiple myeloma [Up to 7 years]

  6. Response to first subsequent multiple myeloma treatment [Up to 7 years]

  7. 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:
No
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

SiteCityStateCountryPostal Code
1Little RockArkansasUnited States
2JacksonvilleFloridaUnited States
3West Palm BeachFloridaUnited States
4AtlantaGeorgiaUnited States
5BostonMassachusettsUnited States
6Ann ArborMichiganUnited States
7Saint LouisMissouriUnited States
8HackensackNew JerseyUnited States
9New YorkNew YorkUnited States
10Chapel HillNorth CarolinaUnited States
11CincinnatiOhioUnited States
12ColumbusOhioUnited States
13PhiladelphiaPennsylvaniaUnited States
14NashvilleTennesseeUnited States
15SeattleWashingtonUnited States
16Box HillAustralia
17ConcordAustralia
18MelbourneAustralia
19Woodville SouthAustralia
20CalgaryAlbertaCanada
21EdmontonAlbertaCanada
22TorontoOntarioCanada
23BrnoCzechia
24Hradec KraloveCzechia
25Praha 2Czechia
26LilleFrance
27NantesFrance
28ParisFrance
29Pierre BeniteFrance
30Rennes CedexFrance
31BerlinGermany
32ChemnitzGermany
33EssenGermany
34HeidelbergGermany
35MainzGermany
36MünchenGermany
37TuebingenGermany
38WürzburgGermany
39HaifaIsrael
40JerusalemIsrael
41Petah TikvaIsrael
42Tel AvivIsrael
43AmsterdamNetherlands
44RotterdamNetherlands
45UtrechtNetherlands
46Nizhny NovgorodRussian Federation
47PetrozavodskRussian Federation
48RyazanRussian Federation
49St-PetersburgRussian Federation
50AnkaraTurkey
51AntalyaTurkey
52IzmirTurkey
53SamsunTurkey
54CardiffUnited Kingdom
55NottinghamUnited Kingdom
56SouthamptonUnited Kingdom
57SurreyUnited Kingdom

Sponsors and Collaborators

  • Janssen Research & Development, LLC

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02316106
Other Study ID Numbers:
  • CR106449
  • 54767414SMM2001
  • 2014-005139-14
First Posted:
Dec 12, 2014
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2021