Clinical trial NCT02335983: Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma
Official title: Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2015-01-12
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key Inclusion Criteria:

1. Newly diagnosed or relapsed multiple myeloma
2. Measureable disease by serum M protein, or urine M protein, or serum free light chain (SFLC) and an abnormal serum kappa lambda ratio (for subjects without detectable serum or urine M-protein), or serum quantitative immunoglobulin A (glgA) (for immunoglobulin (Ig) A subjects whose disease can only be reliable measured by qlgA).
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
4. Left ventricular ejection fraction (LVEF) ≥ 40%

Key Exclusion Criteria:

1. Waldenström macroglobulinemia
2. For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype
3. For relapsed disease:

   1. If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment.
   2. Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy.
   3. Any prior treatment with carfilzomib
4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
5. Plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential)
6. Myelodysplastic syndrome
7. Amyloidosis
8. Prior treatment with carfilzomib or oprozomib

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
measure: Change From Baseline in Hemoglobin Levels
timeFrame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
measure: Change From Baseline in Platelet Count
timeFrame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
measure: Change From Baseline in Neutrophil Count
timeFrame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
measure: Change From Baseline in Bilirubin
timeFrame: Baseline and Cycle 2 day 1
measure: Change From Baseline in Creatinine
timeFrame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Secondary outcomes:
measure: Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
timeFrame: 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
measure: Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
timeFrame: 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
measure: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
timeFrame: 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
measure: Overall Response Rate (ORR)
timeFrame: 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.
measure: Complete Response Rate (CRR)
timeFrame: 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.
measure: Progression-free Survival (PFS)
timeFrame: 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.
measure: Duration of Response (DOR)
timeFrame: 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.
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Bakersfield
country: United States
facility: CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
state: California
city: Burbank
country: United States
facility: Research Site
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center
state: California
city: Fountain Valley
country: United States
facility: Research Site
state: California
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group, Inc.
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology / Oncology Medical Group
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Washington
country: United States
facility: Lombardi Cancer Center, Pediatric Hematology Oncology
state: District of Columbia
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Partners Cancer Care
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Clinical Research Alliance
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: Morton Coleman, MD
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Durham
country: United States
facility: Durham Veterans Affairs Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Sarah Cannon Research Institute
state: Ohio
city: Bend
country: United States
facility: Research Site
state: Oregon
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina, Hollings Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital Cancer Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic, PC
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Wauwatosa
country: United States
facility: Research Site
state: Wisconsin
Study officials:
affiliation: Amgen
name: Amy Kimball, MD
role: STUDY_DIRECTOR
References:
citation: Biran N, Siegel D, Berdeja JG, Raje N, Cornell RF, Alsina M, Kovacsovics T, Fang B, Kimball AS, Landgren O. Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study. Am J Hematol. 2019 Jul;94(7):794-802. doi: 10.1002/ajh.25498. Epub 2019 May 13.