Subcutaneous Daratumumab, Once Weekly Carfilzomib, and Dexamethasone (DKd) in Patients With High-Risk Smoldering Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT04933539|
Recruitment Status : Not yet recruiting
First Posted : June 21, 2021
Last Update Posted : December 1, 2021
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.
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.
People ages 18 and older with smoldering MM that is at high risk of converting to symptomatic MM.
Participants will be screened with:
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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Dexamethasone Drug: Carfilzomib Biological: Daratumumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||59 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Adaptive Study of Subcutaneous Daratumumab, Once Weekly Carfilzomib, and Dexamethasone (DKd) in Patients With High-Risk Smoldering Multiple Myeloma|
|Estimated Study Start Date :||December 6, 2021|
|Estimated Primary Completion Date :||October 31, 2023|
|Estimated Study Completion Date :||October 31, 2027|
Experimental: Arm 1
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)
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
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
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
- Response Rate [ Time Frame: 12 cycles ]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
- Overall Response Rate [ Time Frame: every 6-8 weeks ]The fraction of participants who experience a PR, VGPR, CR or sCR after DKd determined by dividing the number of responders by the total evaluable patients.
- Duration of Response [ Time Frame: every 6-8 weeks ]Time from PR or better until the time of PD. Kaplan-Meier will be utilized
- Biochemical and Symptomatic progression free survival (PFS) [ Time Frame: every 6-8 weeks ]Using Kaplan-Meier method, considering those who biochemically progress or die and those who clinically progress or die, and censoring those who do not
- Durability of MRD negative complete response (CR) [ Time Frame: through 3 years post-treatment ]Sustained negative CR rate 1, 2, 3 years.
- Toxicity evaluation of DKd [ Time Frame: through 30 days post treatment ]Descriptive statistics to determine safety of receiving KRd with daratumumab maintenance
- Overall survival (OS) [ Time Frame: ongoing ]Determined using the Kaplan-Meier method
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04933539
|Contact: NCI Medical Oncology Referral Office||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Mark J Roschewski, M.D.||National Cancer Institute (NCI)|