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

NCT02316106 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR10644954767414SMM20012014-005139-14
• Study Type: interventional
• Target: 123
• Locations: 11 countries
• Sites: 57

Brief Summary

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

Conditions

Multiple Myeloma

Keywords

Smoldering multiple myeloma (SMM); Daratumumab

Outcome Measures

Primary Outcomes (2)

• 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.

  From Cycle 1 Day 1 up to 1.58 years

• 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.

  From Cycle 1 Day 1 up to 2.07 years

Secondary Outcomes (7)

• Minimal Residual Disease (MRD) Negative Rate

  From Cycle 1 Day 1 up to 91.6 months

• Time to Next Treatment (TNT) for Active Myeloma

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

• 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])

  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)

• Progression Free Survival (PFS)

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

• Percentage of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features

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

Study Arms (3)

Arm A (Long Intense)

EXPERIMENTAL

Drug: daratumumab

Arm B (Intermediate)

EXPERIMENTAL

Drug: daratumumab

Arm C (Short Intense)

EXPERIMENTAL

Drug: daratumumab

Interventions

daratumumab DRUG

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).

Arm A (Long Intense)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (57)

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Little Rock, Arkansas, United States

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Jacksonville, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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St Louis, Missouri, United States

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Hackensack, New Jersey, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Nashville, Tennessee, United States

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Seattle, Washington, United States

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Box Hill, Australia

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Concord, Australia

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Melbourne, Australia

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Woodville South, Australia

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Toronto, Ontario, Canada

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Brno, Czechia

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Hradec Králové, Czechia

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Prague, Czechia

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Lille, France

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Nantes, France

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Paris, France

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Pierre-Bénite, France

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Rennes, France

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Berlin, Germany

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Chemnitz, Germany

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Essen, Germany

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Heidelberg, Germany

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Mainz, Germany

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München, Germany

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Tübingen, Germany

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Würzburg, Germany

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Haifa, Israel

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Jerusalem, Israel

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Petah Tikva, Israel

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Tel Aviv, Israel

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Amsterdam, Netherlands

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Rotterdam, Netherlands

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Utrecht, Netherlands

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Nizhny Novgorod, Russia

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Petrozavodsk, Russia

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Ryazan, Russia

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Saint Petersburg, Russia

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Ankara, Turkey (Türkiye)

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Antalya, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Samsun, Turkey (Türkiye)

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Cardiff, United Kingdom

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Nottingham, United Kingdom

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Southampton, United Kingdom

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Surrey, United Kingdom

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Related Publications (3)

• 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.

  PMID: 39652826 DERIVED

• 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.

  PMID: 33474705 DERIVED

• 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.

  PMID: 32024950 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Smoldering Multiple Myeloma

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia

Results Point of Contact

• Title: Sr. Clinical Sciences Group Leader Onc
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: December 12, 2014
• Study Start: May 20, 2015
• Primary Completion: June 2, 2023
• Study Completion: June 3, 2024
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Locations

CZ (3); US (15); GB (4); AU (4); IL (4); DE (8); NL (3); RU (4); FR (5); TU (4); CA (3)