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

NCT04933539 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 21002421-C-0024
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

anti-CD38 monoclonal antibody; Proteasome Inhibitor; Anti-Myeloma Activity; Immunomodulatory Agents; Combination Therapy

Outcome Measures

Primary Outcomes (1)

• Response Rate

  To assess the remission rate of DKd in participants with high-risk (HR) SMM by determining the minimal residual disease (MRD) negative complete response (CR) by flow cytometry (10-5 sensitivity) rate after 12 cycles of therapy

  12 cycles

Secondary Outcomes (6)

• Overall Response Rate

  every 6-8 weeks

• Duration of Response

  every 6-8 weeks

• Biochemical and Symptomatic progression free survival (PFS)

  every 6-8 weeks

• Durability of MRD negative complete response (CR)

  through 3 years post-treatment

• Toxicity evaluation of DKd

  through 30 days post treatment

Study Arms (1)

Arm 1

EXPERIMENTAL

Daratumumab SC (Cycles 1-2: Days 1, 8, 15, 22; Cycles 3-6: Days 1, 15; Cycles =7: Days 1 of the 28-day cycle); Carfilzomib IV (Days 1, 8, 15 of the 28-day cycle); Dexamethasone PO/IV (Days 1, 8, 15, 22 of the 28-day cycle)

Drug: Dexamethasone; Drug: Carfilzomib; Biological: Daratumumab

Interventions

Dexamethasone DRUG

Dexamethasone PO/IV (for Cycles 1-4: Dexamethasone 40 mg IV/PO on days 1, 8, 15, 22; for Cycles =5: Dexamethasone 20 mg IV/PO on days 1, 8, 15, 22); for up to 12 cycles

Arm 1

Carfilzomib DRUG

Carfilzomib IV (for Cycles 1-2: 20 mg/m2 IV on day 1, 56 mg/m2 IV on days 8, 15; Cycles =2: 56/m2 IV on days 1, 8, 15); for up to 12 cycles

Arm 1

Daratumumab BIOLOGICAL

Daratumumab SC 1800 mg (Cycles 1-2: Days 1, 8, 15, 22; Cycles 3-6: Days 1, 15; Cycles =7: Days 1 of the 28-day cycle); up to 36 cycles total

Arm 1

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed smoldering multiple myeloma (SMM) based on the International Myeloma Working Group Criteria:
• Serum M-protein \>=3 g/dl and/or bone marrow plasma cells \>=10 % and \<60%
• Absence of anemia: hemoglobin \>10 g/dl
• Absence of renal failure: serum creatinine \<2.0 mg/dL
• Absence of hypercalcemia: Ca \<10.5 mg/dl or 2.62 mmol/L
• Absence of lytic bone lesion on X-ray, CT, or PET/CT and not more than 1 lesion on spinal MRI (NOTE: At the discretion of the investigator, PET/CT may replace MRI in patients who have a contraindication to MRI.)
• Involved/un-involved light chain ratio must be \< 100 (unless involved light chain is \<=10 mg/dL)
• Measurable disease within the past 4 weeks defined by any one of the following:
• Serum monoclonal protein \>= 0.5 g/dl
• Urine monoclonal protein \>200 mg/24 hour
• Serum immunoglobulin free light chain \>10 mg/dL AND abnormal kappa/lambda serum free light chain ratio (reference 0.26-1.65)
• Because the primary endpoint is MRD (-) remission rate, per the discretion of the Principal Investigator, patients without measurable disease in the serum (e.g., Mspike \<0.5 g/dL) may also be enrolled. This is in line with the most recent IMWG MM response criteria.
• Age \>=18 years.
• ECOG performance status \<=2
• Patients must have adequate organ and marrow function as defined below:

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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; carfilzomib; 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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Elizabeth M Hill, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2021
• First Posted: June 21, 2021
• Study Start: October 31, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 31, 2032
• Last Updated: May 1, 2026

Record last verified: 2026-02-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)