Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02335983
• Other study ID #: CFZ013
• Status: Completed
• Phase: Phase 1
• Start date: April 30, 2015
• Est. completion date: October 28, 2019

Study information

• Verified date: September 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: October 28, 2019
• Est. primary completion date: October 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
• Lenalidomide
Administered orally once daily on days 1-21 of each 28-day cycle.
• Dexamethasone
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.

Locations

Country	Name	City	State
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Aurora	Colorado
United States	University of Colorado	Aurora	Colorado
United States	CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Research Site	Bakersfield	California
United States	Bend Memorial Clinic	Bend	Oregon
United States	Research Site	Bend	Oregon
United States	Dana Farber Partners Cancer Care	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Providence Saint Joseph Medical Center	Burbank	California
United States	Research Site	Burbank	California
United States	Medical University of South Carolina, Hollings Cancer Center	Charleston	South Carolina
United States	Research Site	Charleston	South Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Sarah Cannon Research Institute	Cincinnati	Ohio
United States	Durham Veterans Affairs Medical Center	Durham	North Carolina
United States	Research Site	Durham	North Carolina
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Research Site	Fort Myers	Florida
United States	Compassionate Care Research Group, Inc.	Fountain Valley	California
United States	Research Site	Fountain Valley	California
United States	Research Site	Germantown	Tennessee
United States	Greenville Health System	Greenville	South Carolina
United States	Research Site	Greenville	South Carolina
United States	Saint Francis Hospital Cancer Center	Greenville	South Carolina
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Research Site	Hackensack	New Jersey
United States	Los Angeles Hematology / Oncology Medical Group	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	Research Site	Los Angeles	California
United States	The West Clinic, PC	Memphis	Tennessee
United States	Aurora Health Care, Aurora Cancer Care	Milwaukee	Wisconsin
United States	Research Site	Nashville	Tennessee
United States	Research Site	Nashville	Tennessee
United States	Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Clinical Research Alliance	New York	New York
United States	Memorial Sloan Kettering	New York	New York
United States	Morton Coleman, MD	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Research Site	Sioux Falls	South Dakota
United States	Research Site	Stony Brook	New York
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Research Site	Tampa	Florida
United States	Lombardi Cancer Center, Pediatric Hematology Oncology	Washington	District of Columbia
United States	Research Site	Washington	District of Columbia
United States	Research Site	Wauwatosa	Wisconsin
United States	Florida Cancer Specialists	West Palm Beach	Florida
United States	Research Site	West Palm Beach	Florida
United States	Research Site	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.
Primary	Change From Baseline in Hemoglobin Levels		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Primary	Change From Baseline in Platelet Count		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Primary	Change From Baseline in Neutrophil Count		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Primary	Change From Baseline in Bilirubin		Baseline and Cycle 2 day 1
Primary	Change From Baseline in Creatinine		Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Secondary	Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group		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
Secondary	Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group		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
Secondary	Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group		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
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	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.

External Links

•   AmgenTrials clinical trials website