A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma

Completed · Phase 3

Conditions studied: Smoldering Multiple Myeloma

In brief

The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).

Key facts

Study ID

NCT03301220

Run by

Janssen Research & Development, LLC

People needed

390

Starts

2017-11-07

Expected to finish

2026-05-04

Last updated by the study team

2026-06-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group [IMWG] criteria) for less than or equal to (<=) 5 years with measurable disease at the time of randomization, defined as serum M protein greater than or equal to (>=) 10 gram per liter (g/L) or urine M protein >= 200 milligram per 24 hours (mg/24 hours) or involved serum free light chain (FLC) >=100 milligram per liter (mg/L) and abnormal serum FLC ratio
• Clonal bone marrow plasma cells (BMPCs) >= 10 percentage (%); and at least 1 of the following risk factors; Serum M protein >= 30 g/L, immunoglobulin (Ig)A SMM, immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes (only IgA, IgM, and IgG should be considered in determination for immunoparesis; IgD and IgE are not considered in this assessment), serum involved: uninvolved FLC ratio >= 8 and less than (<) 100, or clonal BMPCs greater than (>) 50% to <60% with measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use highly effective method of contraception
• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization
• During the study and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction

You may not qualify if…

• Multiple myeloma (MM), requiring treatment, defined by any of the following:
• Bone lesions (1 or more osteolytic lesions on low-dose whole body computed tomography [LDCT], positron-emission tomography with computed tomography [PET-CT] or CT). Participants who have benign/post-traumatic bone lesions visible on screening images as well as previous imaging, may be considered for inclusion. Details (diagnosis, location, duration) on benign/post-traumatic pre-existing bone lesions that can be seen on the screening images (example [eg.], old fractures) and were also present on previous imaging are to be reported in the case report form (CRF)
• Hypercalcemia (serum calcium greater than [>]0.25 millimoles per liter [mmol/L] [>1 milligram per deciliter {mg/dL}] higher than upper limit of normal [ULN] or >2.75 mmol/L [>11 mg/dL]). Participants who have clinically stable hypercalcemia attributable to a disease other than multiple myeloma (eg, hyperparathyroidism) may be considered for inclusion after a case by case review by the medical monitor
• Renal insufficiency, preferably determined by creatinine clearance less than (<)40 milliliter per minute (mL/min) measured or estimated using the Modification of Diet in Renal Disease (MDRD), or serum creatinine >177 micromole per liter (μmol/L). Participants who have clinically stable renal insufficiency attributable to a disease other than multiple myeloma (eg, glomerulonephritis) may be considered for inclusion after a case by case review by the medical monitor
• Anemia, defined as hemoglobin <10 gram per deciliter (g/dL) or >2 g/dL below lower limit of normal or both; transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted. Participants who have clinically stable anemia attributable to a disease other than multiple myeloma (eg, thalassemia, vitamin B12 deficiency, iron deficiency) may be considered for inclusion after a case by case review by the medical monitor
• Clonal BMPC percentage >=60%
• Serum FLC ratio (involved:uninvolved) >=100 (the involved FLC must be >=100 mg/L)
• More than 1 focal lesion >=5 millimeter (mm) in diameter by magnetic resonance imaging (MRI)
• Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis
• Exposure to any of the following:
• Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies
• Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs], or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate and denosumab as indicated for osteoporosis is acceptable
• Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 half-lives, whichever is longer, before Cycle 1, Day 1
• Ongoing treatment with corticosteroids with a dose >10 milligram (mg) prednisone or equivalent per day at the time of randomization; or >280 mg cumulative prednisone dose or equivalent for any 4-week period in the year prior to randomization
• Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab), immunomodulators (eg, abatacept, methotrexate, azathioprine, cyclosporine) or other treatments that are likely to interfere with the study procedures or results
• Received treatment (chemotherapy, surgery, et cetera [etc]) for a malignancy (other than SMM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion), which is considered cured with minimal risk of recurrence within 3 years
• Medical or psychiatric condition or disease (for example, active systemic disease [including presence of auto-antibodies], uncontrolled diabetes) 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
• Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies, hyaluronidase, or other human proteins, or their excipients, or known sensitivity to mammalian-derived products (including dairy allergy)

Where it is running

• Innovative Clinical Research Inc — Whittier, California, United States
• Miami Cancer Institute — Miami, Florida, United States
• Emory University — Atlanta, Georgia, United States
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States
• East Jefferson General Hospital — Metairie, Louisiana, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States
• Mayo Clinic — Rochester, Minnesota, United States
• Washington University — St Louis, Missouri, United States
• VA Southern Nevada Healthcare — North Las Vegas, Nevada, United States
• New York Oncology Hematology — Albany, New York, United States
• Stony Brook University Medical Center — Stony Brook, New York, United States
• University of North Carolina — Chapel Hill, North Carolina, United States
• Levine Cancer Institute, Carolinas HealthCare System — Charlotte, North Carolina, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• The Ohio State University — Columbus, Ohio, United States
• OHSU/CHM — Portland, Oregon, United States
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
• Texas Oncology P A 1 — Austin, Texas, United States
• VA North Texas Health Care System — Dallas, Texas, United States
• Texas Oncology P A — Tyler, Texas, United States
• University of Washington — Seattle, Washington, United States
• Hospital Aleman — Buenos Aires, Argentina
• Hospital Italiano de Buenos Aires — Buenos Aires, Argentina
• Arizona Oncology Associates, PC - HAL — Phoenix, Arizona, United States

Full record on ClinicalTrials.gov

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