Clinical Trials /

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

NCT02335983

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b Study of Carfilzomib Administered Once Weekly 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

Clinical Trial IDs

  • ORG STUDY ID: CFZ013
  • NCT ID: NCT02335983

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibPR-171, PR171, Kyprolis® (carfilzomib) for InjectionDose-evaluation: Part 1 - Cohort 1
LenalidomideRevlimid®Dose-evaluation: Part 1 - Cohort 1
DexamethasoneDose-evaluation: Part 1 - Cohort 1

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Dose-evaluation: Part 1 - Cohort 1ExperimentalSubjects will receive a dose level combination regimen of carfilzomib 56 mg/m2, lenalidomide 25 mg, and dexamethasone 40 mg
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Dose-evaluation: Part 1 - Cohort 2ExperimentalSubjects will receive a dose level combination regimen of carfilzomib 70 mg/m2, lenalidomide 25 mg, and dexamethasone 40 mg.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Dose-expansion: Part 2 - Arm 1ExperimentalNewly diagnosed multiple myeloma subjects will receive the regimen selected by the Cohort Safety Review Committee (CSRC) in the Dose-evaluation component.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Dose-expansion: Part 2 - Arm 2ExperimentalRelapsed multiple myeloma subjects will receive the regimen selected by the Cohort Safety Review Committee (CSRC) in the Dose-evaluation component.
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Dose-evaluation: Part 1 - Cohort 4ExperimentalNewly Diagnosed multiple myeloma subjects will receive a 2-step-up regimen of carfilzomib at 56 mg/m2 in Cycle 1 and then at 70 mg/m2 beginning with Cycle 2, lenalidomide 25 mg and dexamethasone 40 mg. (note: all subjects receive 20 mg/m2 carfilzomib on Cycle 1 Day 1)
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
Dose-expansion: Part 2 - Arm 3ExperimentalNewly diagnosed multiple myeloma subjects will receive a combination regimen of carfilzomib 56 mg/m2, lenalidomide 25 mg and dexamethasone 40 mg
  • Carfilzomib
  • Lenalidomide
  • Dexamethasone

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 (qlgA) (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:54 months
Safety Issue:
Description:Safety and tolerability of carfilzomib administered once weekly in combination with lenalidomide and dexamethasone, as defined by the type, incidence, severity, and outcome of Adverse Events (AEs).

Secondary Outcome Measures

Measure:Total Plasma Exposure - Area Under the Curve (AUC)
Time Frame:58 months
Safety Issue:
Description:Total Plasma Exposure - Area Under the Curve (AUC) will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for AUC will be tabulated and summarized (i.e., mean, standard deviation).
Measure:Maximum plasma concentration (Cmax)
Time Frame:58 months
Safety Issue:
Description:Maximum plasma concentration (Cmax) will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for Cmax will be tabulated and summarized (i.e., mean, standard deviation).
Measure:Time to Maximum Plasma Concentration (Tmax)
Time Frame:58 months
Safety Issue:
Description:Time to Peak Concentration (Tmax) will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for Tmax will be tabulated and summarized (i.e., mean, standard deviation).
Measure:Total Plasma Clearance
Time Frame:58 months
Safety Issue:
Description:Total Plasma Clearance will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for Total Plasma Clearance will be tabulated and summarized (i.e., mean, standard deviation).
Measure:Plasma Terminal Half-life
Time Frame:58 months
Safety Issue:
Description:Plasma Terminal Half-life (as appropriate for data collected) will be derived from levels of carfilzomib assayed in Pharmacokinetic (PK) samples. Estimates for Plasma Terminal Half-life will be tabulated and summarized (i.e., mean, standard deviation).
Measure:Overall Response Rate (ORR)
Time Frame:58 months
Safety Issue:
Description:Overall Response Rate (ORR) is defined as the proportion of subjects who achieve a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).
Measure:Complete Response Rate (CRR)
Time Frame:58 months
Safety Issue:
Description:Complete Response Rate (CRR) is defined as the proportion of subjects who achieve a best overall response of either stringent complete response (sCR), complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).
Measure:Progression-free survival (PFS)
Time Frame:58 months
Safety Issue:
Description:Progression-free survival (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.
Measure:Duration of Response (DOR)
Time Frame:58 months
Safety Issue:
Description:Duration of Response (DOR) is defined as the time from the first evidence of confirmed partial response (PR) or better to disease progression or death due to any cause among subjects who respond.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Last Updated

April 26, 2017