A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Carfilzomib; Cyclophosphamide; Dexamethasone
Intervention description: Carfilzomib administered as a 30-minute intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. On Days 1 and 2 of Cycle 1, all participants received carfilzomib at 20 mg/m².; Cyclophosphamide administered orally (PO) at the dose of 300 mg/m² on Days 1, 8, and 15 of each 28-day cycle.; Dexamethasone administered PO or IV at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Intervention MeSH terms: Dexamethasone; Cyclophosphamide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: multiple myeloma

Summary:

      The primary objective was to determine the maximum tolerated dose of carfilzomib given twice
      weekly in combination with cyclophosphamide and dexamethasone for patients with newly
      diagnosed multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Newly diagnosed multiple myeloma

          2. Measurable disease, as defined by 1 or more of the following

               -  Serum M-protein ≥ 0.5 g/dL, or

               -  Urine M-protein ≥ 200 mg/24 hours, or

               -  In subjects without detectable serum or urine M-protein, serum free light chain
                  (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ( κ/λ)
                  ratio

          3. Males and females ≥ 18 years of age

          4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          5. Adequate hepatic function

          6. Left ventricular ejection fraction (LVEF) ≥ 40%

          7. Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L

          8. Platelet count ≥ 50 × 10^9/L

          9. Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min

        Exclusion Criteria:

          1. Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial
             therapy of newly diagnosed multiple myeloma

          2. Multiple myeloma of immunoglobulin M (IgM) subtype

          3. Prior systemic treatment for multiple myeloma

          4. Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the
             equivalent of dexamethasone 160 mg

          5. Known amyloidosis

          6. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV),
             symptomatic ischemia, or conduction abnormalities uncontrolled by conventional
             intervention. Myocardial infarction within 6 months prior to enrollment.

          7. Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or
             hepatitis B (subjects with hepatitis B surface antigen [SAg] or core antibody
             receiving and responding to antiviral therapy directed at hepatitis B are allowed)

          8. Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment

          9. Any other clinically significant medical disease or condition that, in the
             investigator's opinion, may interfere with protocol adherence or a subject's ability
             to give informed consent