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Multiple MyelomaPhase 2NCT02316106

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

A Phase 2 study testing daratumumab in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 57 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
daratumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
123 participants
Where
57 sitesin 11 countries
Study dates
20 May 2015to 3 Jun 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

57 sites in 11 countries.

57 sites in 11 countries

United States15 sites

  • Study site

    Ann Arbor, Michigan

  • Study site

    Atlanta, Georgia

  • Study site

    Boston, Massachusetts

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Cincinnati, Ohio

  • Study site

    Columbus, Ohio

  • Study site

    Hackensack, New Jersey

  • Study site

    Jacksonville, Florida

  • Study site

    Little Rock, Arkansas

  • Study site

    Nashville, Tennessee

  • Study site

    New York, New York

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Seattle, Washington

  • Study site

    St Louis, Missouri

  • Study site

    West Palm Beach, Florida

Other trials in United States

Germany8 sites

  • Study site

    Berlin

  • Study site

    Chemnitz

  • Study site

    Essen

  • Study site

    Heidelberg

  • Study site

    Mainz

  • Study site

    München

  • Study site

    Tübingen

  • Study site

    Würzburg

Other trials in Germany

France5 sites

  • Study site

    Lille

  • Study site

    Nantes

  • Study site

    Paris

  • Study site

    Pierre-Bénite

  • Study site

    Rennes

Other trials in France

Australia4 sites

  • Study site

    Box Hill

  • Study site

    Concord

  • Study site

    Melbourne

  • Study site

    Woodville South

Other trials in Australia

Israel4 sites

  • Study site

    Haifa

  • Study site

    Jerusalem

  • Study site

    Petah Tikva

  • Study site

    Tel Aviv

Other trials in Israel

Russia4 sites

  • Study site

    Nizhny Novgorod

  • Study site

    Petrozavodsk

  • Study site

    Ryazan

  • Study site

    Saint Petersburg

Other trials in Russia

Turkey (Türkiye)4 sites

  • Study site

    Ankara

  • Study site

    Antalya

  • Study site

    Izmir

  • Study site

    Samsun

Other trials in Turkey (Türkiye)

United Kingdom4 sites

  • Study site

    Cardiff

  • Study site

    Nottingham

  • Study site

    Southampton

  • Study site

    Surrey

Other trials in United Kingdom

Canada3 sites

  • Study site

    Calgary, Alberta

  • Study site

    Edmonton, Alberta

  • Study site

    Toronto, Ontario

Other trials in Canada

Czechia3 sites

  • Study site

    Brno

  • Study site

    Hradec Králové

  • Study site

    Prague

Other trials in Czechia

Netherlands3 sites

  • Study site

    Amsterdam

  • Study site

    Rotterdam

  • Study site

    Utrecht

Other trials in Netherlands

About this study

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

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

Read the 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.

Being tested
daratumumab
Keywords
Smoldering multiple myeloma (SMM), Daratumumab
Medical subject headings
Multiple Myeloma, Smoldering Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • daratumumabDrug

    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).

  • daratumumabDrug

    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).

  • daratumumabDrug

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

Study groups in NCT02316106
Study groupRoleWhat they receive
Arm A (Long Intense)ExperimentalNot described
Receives: Drug: daratumumab
Arm B (Intermediate)ExperimentalNot described
Receives: Drug: daratumumab
Arm C (Short Intense)ExperimentalNot described
Receives: Drug: daratumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Achieved a Complete Response (CR) by International Myeloma Working Group (IMWG) Criteria

    Percentage of participants who achieved a CR by IMWG Criteria were reported. CR was defined as CR plus stringent complete Response (sCR) by IMWG criteria. Per IMWG criteria, CR response was defined as a negative immunofixation on the serum and urine, and less than (<) 5 percentage (%) plasma cells in bone marrow; sCR was defined as CR plus normal free light chain (FLC) ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.

    Measured: From Cycle 1 Day 1 up to 1.58 years

  2. Progressive Disease or Death Rate

    Progressive disease (PD) or death rate were reported. PD or death rate per patient-year was defined as number of events (PD or death) divided by total progression-free survival (PFS) for all participants.

    Measured: From Cycle 1 Day 1 up to 2.07 years

Secondary outcomes (7)

  1. Minimal Residual Disease (MRD) Negative Rate

    MRD negative rate were reported. The MRD negativity rate was defined as the percentage of participants with a CR or better response who had negative MRD (10^-4 and 10^-5) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates at any time after the randomization and prior to progressive disease, subsequent therapy.

    Measured: From Cycle 1 Day 1 up to 91.6 months

  2. Time to Next Treatment (TNT) for Active Myeloma

    Time to next treatment (TNT) for active myeloma were reported. Time to next treatment was defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment. Kaplan-Meier estimate was used.

    Measured: From randomization (Day -5) up to the date of first subsequent antimyeloma treatment (up to 7.89 years)

  3. Percentage of Participants Who Achieved Partial Response or Better Response (Stringent Complete Response [sCR] Plus Complete Response [CR] Plus Very Good Partial Response [VGPR] or a Partial Response [PR])

    Per IMWG criteria, CR: was defined as a negative immunofixation on serum and urine, and <5% plasma cells in bone marrow; sCR: CR plus normal FLC ratio, and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hours; PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of >=50% in difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein were not measurable and serum free light assay was also not measurable, >=50% reduction in bone marrow plasma cells was required in place of M-protein, provided baseline bone marrow plasma cells percentage was >=30%.

    Measured: From start of the treatment (Cycle 1 Day 1) until confirmed PD, death, start of new anticancer therapy, withdrawal of consent, lost to follow-up, or end of the study, whichever occurred first (up to 7.89 years)

  4. Progression Free Survival (PFS)

    PFS: time from dates of randomization to initial documented PD per Sixty percent, bone marrow plasma cells (BMPC), Light chains, focal lesions per MRI, elevated Calcium, Renal failure, Anemia, Bone lesions (SLiM-CRAB) criteria, or date of death, whichever was first. SLiM-CRAB criteria: clonal BM PCs percentage (%): >=60%, Involved: uninvolved serum free LC ratio >=100, >1 focal lesion on MRI studies, calcium:>0.25 millimole/liter (mmol/L)(>1 mg/dL) higher than upper limit of normal or >2.75 mmol/L (>11 mg/dL); creatinine clearance <40 mL/min or serum creatinine >177 micromole/liter (>2 mg/dL); hemoglobin <10 g/dL(<6.5 mmol/L) or >2 g/dL(>1.25 mmol/L) lower than lower limit of normal;>1 osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT). Kaplan-Meier estimate was used.

    Measured: From randomization (Day -5) until disease progression or death whichever occurred first (up to 7.89 years)

  5. Percentage of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features

    Percentage of participants with symptomatic multiple myeloma with adverse prognostic features were reported. The International Staging System (ISS) for multiple myeloma (MM) was based on serum beta-2 microglobulin (S beta-2M) and serum albumin; that is, participants progressed to symptomatic multiple myeloma (SymT MM) with stage III (S beta2M>= 5.5 mg/L) of ISS, Participants progressed to SymT MM with adverse cytogenetic characteristics (ACC), participants progressed to SymT MM with stage III of ISS or adverse cytogenetic characteristics. Adverse cytogenetic characteristics included Fluorescence in situ hybridization (FISH) findings of del(17p13), t(14;16), t(4;14), amp(1q21) or karyotype findings of t(4;14), del(17p) or a combination of these.

    Measured: From start of treatment (Cycle 1 Day 1) until PD or prior to any subsequent anti-Multiple myeloma therapy (up to 7.89 years)

  6. Number of Participants With Response to First Subsequent Multiple Myeloma Treatment

    Response (IMWG Criteria) to first subsequent MM treatment: sCR: CR + normal FLC ratio and absence of clonal plasma cells by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: a negative immunofixation on serum and urine, and <5% plasma cells in BM; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100mg/24 hours; PR:>=50% reduction of serum M-protein and >=90% reduction in urine M-protein in 24 hour or to <200 mg/24 hours; if serum and urine M-protein were not measurable, a decrease of >=50% difference between involved and uninvolved FLC levels was required instead of M-protein criteria. If serum and urine M-protein and serum free light assay was also not measurable, >=50% reduction in bone marrow plasma cells was required instead of M-protein, provided bone marrow plasma cells percentage was >=30%.

    Measured: From Cycle 1 Day 1 up to 7.89 years

  7. Overall Survival

    Overall Survival (OS) was defined as the time from the date of randomization to the date of death. Median OS was estimated by using the Kaplan-Meier method.

    Measured: From randomization (Day -5) till death (up to 7.89 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Dec 2014 (estimated)
  2. Study start20 May 2015
  3. Primary completion2 Jun 2023
  4. Study completion3 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
123 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02316106
Sponsor's protocol ID
CR106449
Other IDs
54767414SMM2001, 2014-005139-14, 2014
Status last verified
Apr 2026
First submitted
10 Dec 2014
Last updated
23 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Landgren O, Chari A, Cohen YC, Spencer A, Voorhees PM, Sandhu I, Jenner MW, Smith D, Cavo M, van de Donk NWCJ, Beksac M, Moreau P, Goldschmidt H, Vieyra D, Sha L, Li L, Rousseau E, Dennis R, Carson R, Hofmeister CC. Efficacy and safety of daratumumab in intermediate/high-risk smoldering multiple myeloma: final analysis of CENTAURUS. Blood. 2025 Apr 10;145(15):1658-1669. doi: 10.1182/blood.2024025897.

    PubMed 39652826

  • 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.

    PubMed 33474705

  • 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.

    PubMed 32024950

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing daratumumab in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 57 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites in United States, Germany, France, Australia, Israel and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Achieved a Complete Response (CR) by International Myeloma Working Group (IMWG) Criteria (time frame: From Cycle 1 Day 1 up to 1.58 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02316106, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.

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