A Study of Carfilzomib Plus Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma at US Community Oncology Centers
Condition: Relapsed or Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Carfilzomib
Intervention description: Dexamethasone will be taken orally or by IV infusion at a dose of 20 mg once-daily on days 1, 2, 8, 9, 15, 16, 22, and 23 of cycles 1-6, and at a dose 40 mg once-daily on days 1, 8, 15 of cycles 7-12.; Carfilzomib will be administered at 20 mg/m² on days 1 and 2 of the first cycle. After that, carfilzomib will be administered at 56 mg/m² on days 8, 9, 15, and 16 of the first cycle, and then on days 1, 2, 8, 9, 15, and 16 on each 28-day cycle for the cycles 2 through 6. Starting with cycle 7 through cycle 12, carfilzomib will be administered at 70 mg/m² on days 1, 8, and 15 of each 28-day cycle. All
Intervention MeSH terms: Dexamethasone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective was to describe the safety profile of carfilzomib plus dexamethasone
      regimen in adults with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines
      of therapy at study entry.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has provided informed consent prior to initiation of any study specific
             activities/procedures.

          -  Males or females greater than or equal to 18 years of age.

          -  Relapsed MM after last treatment or refractory while receiving non-proteasome
             inhibitor therapy.

          -  Measurable disease with at least 1 of the following assessed within 21 days prior to
             enrollment:

               -  Immunoglobulin G (IgG) MM: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL

               -  IgA, IgD, IgE multiple myeloma: serum M protein level ≥ 0.5 g/dL

               -  Urine M-protein ≥ 200 mg per 24 hours

               -  In subjects without measurable serum or urine M-protein, serum free light chain
                  (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda
                  ratio.

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.

          -  Subjects must have at least partial response (PR) to at least 1 line of prior therapy.

          -  Subjects must have received at least 1 but not more than 3 prior lines of therapy for
             MM (induction therapy followed by stem cell transplant and consolidation/maintenance
             therapy will be considered as 1 line of therapy).

          -  Prior therapy with a proteasome inhibitor (PI) is allowed as long as the subject had
             at least a PR to most recent therapy with PI, was not removed due to toxicity (except
             for neuropathy), did not relapse within 60 days from discontinuation of PI, and will
             have at least a 6-month PI treatment-free interval from last dose received until
             enrollment. (Subjects may receive maintenance therapy with drugs that are not PI
             during this 6-month PI treatment-free interval).

        Exclusion Criteria:

          -  Waldenström macroglobulinemia.

          -  Multiple myeloma of IgM subtype.

          -  POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes).

          -  History of plasma cell leukemia.

          -  Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of
             amyloid plaques found on biopsy would be eligible if all other criteria are met).

          -  Subjects with nephrotic range proteinuria (greater than or equal to 3 g albumin for 24
             hours urine OR greater than or equal to 2 g albumin/1 g of creatinine on a random
             urine specimen).

          -  Myelodysplastic syndrome.

          -  History of other malignancy within the past 5 years, with the following exceptions:

               -  Malignancy treated with curative intent and with no known active disease present
                  for greater than or equal to 3 years before enrollment and felt to be at low risk
                  for recurrence by the treating physician.

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease.

               -  Adequately treated cervical carcinoma in situ without evidence of disease.

               -  Adequately treated breast ductal carcinoma in situ without evidence of disease.

               -  Prostatic intraepithelial neoplasia without evidence of prostate cancer.

               -  Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
                  situ.

               -  Treated medullary or papillary thyroid cancer.

               -  Similar neoplastic conditions with an expectation of greater than 95% five-year
                  disease-free survival.

          -  Known human immunodeficiency virus (HIV) infection, hepatitis C infection (subjects
             with hepatitis C that achieve a sustained virologic response following antiviral
             therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface
             antigen or core antibody that achieve sustained virologic response with antiviral
             therapy directed at hepatitis B are allowed).

          -  Acute or chronic graft-versus-host disease (any grade).

          -  Acute active infection requiring systemic antibiotics, antifungal, antiviral (except
             antiviral therapy directed at hepatitis B) agents within 14 days prior to enrollment.

          -  Known cirrhosis.

          -  Significant neuropathy (grades 3 to 4, or grade 2 with pain) within 14 days prior to
             enrollment.

          -  Subjects with pleural effusions requiring thoracentesis or ascites requiring
             paracentesis within 14 days prior to enrollment.

          -  Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or
             diastolic ≥ 100 mmHg. Subjects with controlled hypertension are eligible.

          -  Hepatic dysfunction within 21 days prior to enrollment: bilirubin 1.5 times the upper
             limit of normal (ULN) aspartate aminotransferase (AST) or alanine aminotransferase
             (ALT) 3 times the ULN

          -  Active congestive heart failure with or without reduced ejection fraction (New York
             Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled
             arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening
             ECG with corrected QT interval (QTc) of greater than 470 msec, pericardial disease,
             myocardial infarction within 4 months prior to enrollment.

          -  Known chronic obstructive pulmonary disease.

          -  Known interstitial pneumonitis.

          -  Immunotherapy within 21 days prior to enrollment.

          -  Chemotherapy with approved anticancer therapeutic within 21 days prior to enrollment.

          -  Glucocorticoid therapy (prednisone greater than 30 mg/day or equivalent) within 14
             days prior to enrollment.

          -  Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an
             extended field involving a significant volume of bone marrow within 21 days prior to
             enrollment (ie, prior radiation must have been to less than 30% of the bone marrow).

          -  Major surgery (except kyphoplasty) within 28 days prior to enrollment.

          -  Autologous or allogeneic stem cell transplant within 90 days prior to enrollment.

          -  Contraindication to dexamethasone.

          -  Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize
             carfilzomib).

          -  Intolerance to intravenous (IV) hydration.

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 30 days since ending treatment on another investigational device or drug
             study(ies). Other investigational procedures while participating in this study are
             excluded.

          -  Hepatic dysfunction within 21 days prior to enrollment: bilirubin greater than or
             equal to 1.5 times the upper limit of normal (ULN); aspartate aminotransferase (AST)
             or alanine aminotransferase (ALT) greater than or equal to 3 times the ULN.

          -  Left ventricular ejection fraction less than 40% assessed by transthoracic
             echocardiogram.

          -  Severe valvular disease assessed by transthoracic echocardiogram.

          -  Severe right-ventricular dysfunction assessed by transthoracic echocardiogram.

          -  Right-ventricular systolic pressure greater than 40 mm Hg assessed by transthoracic
             echocardiogram.

          -  Screening absolute neutrophil count (ANC) should be independent of growth factor
             support for greater than or equal to 1 week.

          -  Hemoglobin less than 80 g/L within 21 days prior to enrollment. Use of erythropoietic
             stimulating factors and red blood cell (RBC) transfusions per institutional guidelines
             is allowed, however most recent RBC transfusion may not have been done within 7 days
             prior to obtaining screening hemoglobin.

          -  Platelet count < 50 x 10^9/L (≤ 30 x 10^9/L if myeloma involvement in the bone marrow
             is > 50%) within 21 days prior to enrollment. Subjects should not have received
             platelet transfusions for at least 1 week prior to obtaining the screening platelet
             count.

          -  Estimated glomerular filtration rate (GFR) less than 30 mL/min/1.73 m^2 (per the
             Chronic Kidney Disease Epidemiology Collaboration formula) within 21 days prior to
             enrollment.