The purpose of the study is to assess the safety, tolerability and activity of a once-weekly regimen of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
107
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Administered orally once daily on days 1-21 of each 28-day cycle.
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
Number of Participants With Adverse Events (AEs)
Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
Time frame: From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
Change From Baseline in Hemoglobin Levels
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Platelet Count
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Neutrophil Count
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Bilirubin
Time frame: Baseline and Cycle 2 day 1
Change From Baseline in Creatinine
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Research Site
Bakersfield, California, United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
Bakersfield, California, United States
Research Site
Burbank, California, United States
Providence Saint Joseph Medical Center
Burbank, California, United States
Research Site
Fountain Valley, California, United States
Compassionate Care Research Group, Inc.
Fountain Valley, California, United States
Research Site
Los Angeles, California, United States
Research Site
Los Angeles, California, United States
Los Angeles Hematology / Oncology Medical Group
Los Angeles, California, United States
Research Site
Whittier, California, United States
...and 49 more locations
Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time frame: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time frame: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Time frame: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
Overall Response Rate (ORR)
Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy. Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation.
Time frame: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Complete Response Rate (CRR)
Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC.
Time frame: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Progression-free Survival (PFS)
PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause. Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia. PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment.
Time frame: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
Duration of Response (DOR)
Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment.
Time frame: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.