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

NCT ID: NCT02316106

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-20
• Study Completion Date: 2024-06-03

Brief Summary

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

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (Long Intense)

Group Type: EXPERIMENTAL

daratumumab

Intervention Type: 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 B (Intermediate)

Group Type: EXPERIMENTAL

daratumumab

Intervention Type: DRUG

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).

Arm C (Short Intense)

Group Type: EXPERIMENTAL

daratumumab

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

daratumumab

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Little Rock, Arkansas, United States

Jacksonville, Florida, United States

West Palm Beach, Florida, United States

Atlanta, Georgia, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

St Louis, Missouri, United States

Hackensack, New Jersey, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Philadelphia, Pennsylvania, United States

Nashville, Tennessee, United States

Seattle, Washington, United States

Box Hill, , Australia

Concord, , Australia

Melbourne, , Australia

Woodville South, , Australia

Calgary, Alberta, Canada

Edmonton, Alberta, Canada

Toronto, Ontario, Canada

Brno, , Czechia

Hradec Králové, , Czechia

Prague, , Czechia

Lille, , France

Nantes, , France

Paris, , France

Pierre-Bénite, , France

Rennes, , France

Berlin, , Germany

Chemnitz, , Germany

Essen, , Germany

Heidelberg, , Germany

Mainz, , Germany

München, , Germany

Tübingen, , Germany

Würzburg, , Germany

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Tel Aviv, , Israel

Amsterdam, , Netherlands

Rotterdam, , Netherlands

Utrecht, , Netherlands

Nizhny Novgorod, , Russia

Petrozavodsk, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Ankara, , Turkey (Türkiye)

Antalya, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Samsun, , Turkey (Türkiye)

Cardiff, , United Kingdom

Nottingham, , United Kingdom

Southampton, , United Kingdom

Surrey, , United Kingdom

Countries

United States; Australia; Canada; Czechia; France; Germany; Israel; Netherlands; Russia; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39652826 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33474705 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32024950 (View on PubMed)

Other Identifiers

54767414SMM2001

Identifier Type: OTHER

Identifier Source: secondary_id

2014-005139-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR106449

Identifier Type: -

Identifier Source: org_study_id