Subcutaneous Daratumumab, Once Weekly Carfilzomib, and Dexamethasone (DKd) in Patients With High-Risk Smoldering Multiple Myeloma

Running, not enrolling · Phase 2

Conditions studied: Multiple Myeloma

In brief

Background: Multiple myeloma (MM) is a tumor in which malignant plasma cells accumulate in the bone marrow. It can cause organ damage and is not curable. Researchers want to see if a combination drug treatment can help. Objective: To try to prevent or slow down developing MM and its associated organ damage by treating it while still in the smoldering phase with a mix of drugs known as DKd. Eligibility: People ages 18 and older with smoldering MM that is at high risk of converting to symptomatic MM. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Bone survey (x-rays of their bones) Spinal magnetic resonance imaging Bone marrow biopsy (a needle is used to remove bone marrow from their hipbone) Electrocardiogram (to check heart function) Lung function tests Treatment will be given in 28-day cycles. Participants will get daratumumab by injection under the skin. They will get carfilzomib intravenously (IV) through a tube inserted in a vein. They will get dexamethasone as oral tablets or as an IV. They will get all 3 drugs for 8 or 12 cycles. Then they will get daratumumab alone for up to 24 cycles. They may have stem cells collected. Participants will have frequent study visits. At these visits, they will repeat some screening tests. They will complete questionnaires. They will have imaging scans. For these scans, they may receive an oral or IV contrast. Participants will have a follow-up visit 30 days after treatment ends. Then they will have visits every 3-12 months. They will be followed on this study for life.

Key facts

Study ID: NCT04933539
Run by: National Cancer Institute (NCI)
People needed: 14
Starts: 2022-10-31
Expected to finish: 2032-10-31
Last updated by the study team: 2026-08-07

Who can join

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

You may not qualify if…

Patients who are receiving any other investigational agents.
Prior therapy for SMM. At the discretion of the investigator, exceptions might be made depending on prior treatments received and response to those treatments, provided that by the start of protocol therapy, there will be a 4-week washout period. Exceptions will not be made for patients who have received the current DKd with daratumumab maintenance regimen nor any other regimen consisting of daratumumab and a proteasome inhibitor (e.g., bortezomib, ixazomib). Treatment with corticosteroids for other indications is permitted.
Contraindication to any concomitant medication, including support/prophylaxis for infusion reaction, antiviral, antibacterial, anticoagulation or tumor lysis given prior to therapy.
Patient has either of the following:
-Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
--Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. NOTE: Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
Seropositive for human immunodeficiency virus (HIV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load for at least the 3 months prior to enrollment are eligible for this trial.
Active hepatitis B infection. NOTE: Patients who are hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive will need to have a negative HBV PCR result before enrollment. Those with a positive PCR for hepatitis B are excluded.
Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib or daratumumab or other agents used in study.
Current uncontrolled hypertension (chronic systolic blood pressures >160 mm Hg) or diabetes (chronic clinical signs/symptoms of hyperglycemia and/or an A1c value >9%).
Significant cardiovascular disease with NYHA Class II, III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia.
No studies of carfilzomib or daratumumab have been conducted on nursing individuals and it is not known if it is excreted in milk. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, nursing should be discontinued if the mother is treated with carfilzomib/daratumumab.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, venous thromboembolic disease, hemorrhage, pulmonary fibrosis, pneumonitis, or psychiatric illness/social situations that would limit compliance with study requirements.

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.