Comprehensive Analysis of Clinical Parameters That May Inform the Choice of Dose Regimen for Carfilzomib 20/27mg/m2 or 20/56mg/m2 With and Without Dexamethasone (20200381)

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Other
• If ‘other’, further details on the scope of the study:
  Identify clinical parameters that may inform choice of carfilzomib dose regimen.
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Retrospective, post-hoc, pooled analysis

Study drug and medical condition

• Medical condition to be studied:
  Plasma cell myeloma
• Additional medical condition(s):
  Relapsed or refractory multiple myeloma (RRMM)

Population studied

• Short description of the study population:
  Patients with refractory relapsed multiple myeloma (RRMM) who received consistent twice-weekly K treatment with K27, Kd27, K56, or Kd56 identified from the Amgen-sponsored clinical trial between 2005 and 2019.; Inclusion Criteria:; Step 1: Identify all Amgen acquired or sponsored studies in Onyx-owned or RAVE database until 14 July 2019.; Step 2: Within those databases, identify all clinical studies that enrolled subjects with RRMM; · These subjects may have received any number of prior lines of therapy; Step 3: Among those clinical studies, identify all subjects treated with K dosing frequency of twice a week at the start of each week for three of the four-week cycles (days 1, 2, 8, 9, 15, 16 for each 28-day cycle) for all cycles of treatment.; Step 4: Separate these subjects based on treatment of K27, Kd27, K56, or Kd56. If the regimen in the individual clinical trial dictates that the first and/or second cycle of K therapy is 15mg/m2 or 20mg/m2, but 27mg/m2 is specified for subsequent K cycles of therapy, then the clinical trial will be included for subjects who receive K at 27mg/m2 with or without dexamethasone.; · If the regimen in the clinical trial dictates that the first cycle of K therapy is 27mg/m2, but 56mg/m2 is specified for subsequent K cycles of therapy, then the; clinical trial will be included for subjects who receive K at 56 mg/m2 with or without dexamethasone.; · Therapeutic dexamethasone dosing will be based on the subject receiving at least 20mg per week.; ; Exclusion Criteria:; Exclude any subjects duplicated among the different carfilzomib regimens.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Renal impaired

  Hepatic impaired

  Immunocompromised

  Other
• Special population of interest, other:
  Multiple Myeloma patients
• Estimated number of subjects:
  1817

Study design details

• Main study objective:
  Describe the benefit-risk profile for each pre-specified K regimen (K27, Kd27, K56, Kd56) based on the clinical parameters that are associated with efficacy and safety outcomes from the pooled data meeting the criteria for sample size and completeness of covariates.
• Outcomes:
  •Progression free Survival (PFS) •Objective Response •Grade 3 or higher adverse events and Serious Adverse Events (SAE) for the following key risks that may impact the overall benefit risk profile of carfilzomib: oCardiac failure (SMQN) oAcute Renal failure (SMQN) oHypertension (SMQN) oCardiac events •Fatal adverse events, Compare the same efficacy and safety outcomes as the primary outcome for K dosing regimens with dexamethasone (Kd27 versus Kd56).
• Data analysis plan:
  Data from the 13 clinical trials will be pooled for the analysis of clinical parameters that may inform the choice of K dose regimen. All analyses will be descriptive. No formal hypothesis testing is planned for the efficacy and safety comparison between carfilzomib dosing regimens.