NCT04933539

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

A Phase 2 Adaptive Study of Subcutaneous Daratumumab, Once Weekly Carfilzomib, and Dexamethasone (DKd) in Patients With High-Risk Smoldering Multiple Myeloma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Background: Smoldering multiple myeloma (SMM) is a precursor condition to MM defined by the clinical parameters of M-protein \>=3.0 g/dL or bone marrow plasma cells \>=10%, and absence of end organ disease. Patients with high-risk SMM have a risk of progression to MM of 72-75% in 5 years with median time to progression of \<2 years. The current standard of care for SMM is close follow-up without treatment, until symptomatic MM develops. However, International Myeloma Working Group (IMWG) recommends Preventive clinical trials need to be considered for patients with high risk smoldering myeloma. Carfilzomib is a proteasome inhibitor and daratumumab is an anti-CD38 monoclonal antibody, both with potent anti-MM effects. Objectives: To assess the remission rate of daratumumab, carfilzomib, and dexamethasone (DKd) in patients with high-risk (HR) smoldering multiple myeloma (SMM) by determining the minimal residual disease (MRD) negative complete response (CR) rate by up to 12 cycles of induction therapy using flow cytometry. Eligibility: SMM according to the IMWG definition; i.e.: 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 lesions \<=1 focal lesion on MRI Involved/un-involved light chain ratio \<100 High-risk SMM per Mayo Clinic, Spanish PETHEMA, or the Rajkumar, Landgren, Mateos criteria Age \>=18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate laboratory parameters Design: Single arm trial of combination therapy (daratumumab, carfilzomib, and dexamethasone) followed by daratumumab maintenance monotherapy (DKd-D) for high-risk SMM. Participants will receive 8 cycles of DKd induction combination therapy. After 8 cycles, participants who have not attained an MRD negative remission will receive 4 additional cycles of DKd. Each cycle consists of 28-days. After 4 cycles of induction therapy, transplant eligible participants may choose to undergo stem cell collection for storage. After induction with DKd, participants will receive daratumumab maintenance therapy for 24 cycles. Participants will have routine blood work with SPEP and free light chains at the start of each cycle during the induction phase. Laboratory evaluations may be spread out to every 3-6 months during the maintenance and follow-up phases. Pre-treatment, post-treatment and follow-up bone marrow biopsies will be obtained for confirmation of diagnosis, response and correlative studies. Participants will also undergo evaluation for MRD at regular interval time points, using multi-parametric flow cytometry, FDG PET-CT, and Diffusion Weighted Whole Body (DW-MRI). The statistical analysis of the primary endpoint, MRD negativity, will be performed at the end of induction therapy.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Dexamethasone	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
DRUG	Carfilzomib	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
BIOLOGICAL	Daratumumab	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

Timeline

• Start date: 2022-10-31
• Primary completion: 2026-08-31
• Completion: 2032-10-31
• First posted: 2021-06-21
• Last updated: 2026-04-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study