Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia
Condition: Waldenstrom's Macroglobulinemia
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: Dexamethasone; Carfilzomib; Rituximab
Intervention description: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8; 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8; 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Intervention MeSH terms: Dexamethasone; Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: WM; untreated; symptomatic

Summary:

      Carfilzomib is a drug that has shown anti-tumor activity by inhibiting the proteasome within
      the cell, which is responsible for degrading or breaking down a wide variety of proteins.
      Carfilzomib has not been approved by the FDA.

      Rituximab and dexamethasone are often used to treat Waldenstrom's Macroglobulinemia (WM),
      alone or in combination with other drugs. Combinations with rituximab, dexamethasone and
      proteasome inhibitors, like carfilzomib, show high levels of activity in WM patients.

      In this research study, the investigators are testing the safety and efficacy of Carfilzomib
      when used along with Rituximab and Dexamethasone as a possible treatment for Waldenstrom's
      Macroglobulinemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Waldenstrom's Macroglobulinemia

          -  Symptomatic disease

          -  Measurable disease

          -  Life expectancy of greater than 12 weeks

          -  Adequate organ and marrow function

          -  CD20 positive based on any previous performed bone marrow immunohistochemistry or flow
             cytometric analysis

          -  Disease free of prior malignancies for >/= 5 years with the exception of currently
             treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the
             cervix or breast

        Exclusion Criteria:

          -  More than one prior therapy

          -  Previous therapy with a proteasome inhibitor or rituximab

          -  Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
             prior to entering the study or not recovered from adverse events due to agents
             administered more than 4 weeks earlier

          -  Currently receiving treatment for any malignancy

          -  Major surgery within 21 days prior to study entry

          -  Acute active infection requiring treatment (systemic antibiotics, antivirals, or
             antifungals) within 14 days prior to study entry

          -  Uncontrolled hypertension or uncontrolled diabetes

          -  Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
             study entry

          -  Known history of allergy to Captisol

          -  Receiving any other study agents

          -  Known brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to carfilzomib, rituximab, and/or dexamethasone

          -  Contraindication to any of the required concomitant drugs or supportive treatments,
             including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
             drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant or lactating

          -  HIV-positive on combination antiretroviral therapy