This study evaluates the use of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Subjects will receive treatment in 3 phases - induction (6 cycles), consolidation (6 cycles), and maintenance (12 cycles). Each cycle is 28 days.
This study is a multi-center phase 2 study of carfilzomib, lenalidomide, daratumumab, and dexamethasone in subjects with high-risk smoldering multiple myeloma (SMM). Myeloma remains incurable with the current approaches. The typical natural history of myeloma is one of repeated relapses, accompanied by genetic evolution and development of new abnormalities, which are often responsible for drug resistance. The presence of a precursor phase of smoldering myeloma, and the ability to identify those at the highest risk of progression, sets the stage to examine the possibility that we can cure the disease through early intervention. In order to potentially achieve this, we need to develop a highly effective combination that includes the most active drugs from different classes. Carfilzomib in combination with lenalidomide and dexamethasone results in high response rates and deep responses in subjects with newly diagnosed myeloma. Daratumumab in combination with lenalidomide results in high response rates in relapsed refractory disease. All these drugs are well tolerated and subjects are able to stay on them long term as a maintenance treatment. The combination of the carfilzomib, lenalidomide, daratumumab and dexamethasone presents the potential to enhance the effectiveness of the regimens. We hypothesize that this combination will lead to deep response including a higher proportion of minimal residual disease (MRD) negative disease among those with high risk smoldering myeloma and may translate into cure or long term disease quiescence.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
87
56 mg/m2 IV given on days 1, 8, and 15 of each cycle during induction and consolidation phases of the study.
25 mg po given on days 1-21 of each cycle during the induction and consolidation phases. 10 mg po given on days 1-21 of each cycle during the maintenance phase.
16 mg/kg IV given on days 1, 8, 15, and 22 of cycles 1-2; days 1 and 15 of cycles 3-6; day 1 of cycle 7-12; Day 1 of odd cycles for cycles 13-24.
Moffitt Cancer Center
Tampa, Florida, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
Stringent complete response rate
A confirmed sCR on 2 consecutive evaluations at any time during the course of treatment.
Time frame: During treatment
MRD negativity after each treatment phase
MRD negativity after induction, consolidation, and maintenance
Time frame: 6 months, 12 months, and 2 years
MRD negativity at 1 year post treatment
Persistent MRD negativity rate will be evaluated at 1 year after completion of planned treatment consisting of induction, consolidation, and maintenance.
Time frame: 1 year post treatment
Overall Survival
time of registration to death due to any cause
Time frame: up to 10 years post registration
Progression-free survival
the time from registration to the earliest date of documentation of disease progression or death due to any cause
Time frame: up to 10 years post registration
Adverse events
all eligible subjects that have initiated treatment will be considered evaluable for assessing adverse even rates. The maximum grade for each type of adverse event will be recorded. Relationship to trial treatment will be taken into consideration.
Time frame: 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
40 mg oral given on days 1, 8, 15, and 22 of cycles 1-6 20 mg oral given on days 1, 8, 15, and 22 of cycles 7-12
University of Kansas Cancer Center
Westwood, Kansas, United States
University of Maryland Medical Center
Baltimore, Maryland, United States
Mayo Clinic
Rochester, Minnesota, United States
Weill Cornell Medicine
New York, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Swedish Cancer Institute
Seattle, Washington, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States