Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Intervention: bortezomib; cyclophosphamide; dexamethasone
Intervention description: First 33 patients: 1.3 mg/m^2 IV Days 1, 4, 8 & 11
Remaining 30 patients: 1.5 mg/m^2 IV Days 1, 8, 15 & 22; 300mg/m^2 PO days 1, 8, 15 & 22; First 33 patients: 40 mg PO Days 1-4, 9-12, 17-20
Remaining 30 patients: 40 mg PO Days 1-4, 9-12, 17-20 for cycles 1-2; Days 1, 8, 15, 22 for cycle 3+2 for cycle 3 and beyond
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage II multiple myeloma; stage III multiple myeloma

Summary:

      RATIONALE: Drugs used in chemotherapy such as cyclophosphamide and dexamethasone work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the
      enzymes needed for cell growth. Giving cyclophosphamide and dexamethasone together with
      bortezomib may kill more cancer cells.

      PURPOSE: This phase II trial is studying giving cyclophosphamide and dexamethasone together
      with bortezomib to see how well it works in treating patients with newly diagnosed multiple
      myeloma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Confirmed diagnosis of symptomatic multiple myeloma

               -  Durie Salmon stage 2 or higher

               -  Previously untreated multiple myeloma (including immunomodulatory drugs such as
                  thalidomide) with the exception of bisphosphonates

          -  Evaluable or measurable disease, as defined by at least one of the following:

               -  Serum monoclonal protein ≥ 1 g/dL (measurable disease)

               -  Urine monoclonal protein ≥ 200 mg/24 hours by protein electrophoresis (measurable
                  disease)

               -  Serum-free light chains (FLC) ≥ 10 mg/dL, kappa or lambda, accompanied by an
                  abnormal kappa/lambda ratio

        Serum FLC's should only be used for patients without measurable serum or urine m-spike

        - Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)

        * Patients diagnosed with smoldering myeloma or monoclonal gammopathy of undetermined
        significance are not eligible

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2

             - ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator

          -  Total bilirubin normal OR direct bilirubin ≤ 2.0 mg/dL

          -  Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)

          -  AST ≤ 3 times ULN

          -  Creatinine ≤ 3.5 mg/dL

          -  Absolute neutrophil count ≥ 1,000/mm³ without transfusion or growth factor

          -  Platelet count ≥ 100,000/mm³ without transfusion or growth factor

          -  Willingness and the physical and mental capability to provide written informed consent

          -  Willingness to return to Mayo Clinic Arizona/Princess Margaret Hospital for follow-up

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

        Exclusion criteria:

          -  Peripheral sensory neuropathy ≥ grade 2 as defined by National Cancer Institute (NCI)
             Common Terminology for Common Adverse Events (CTCAE) version 3.0

          -  Known hypersensitivity to compounds containing boron or mannitol

          -  Active uncontrolled infection

          -  Severe cardiac comorbidity including but not limited to:

               -  New York Heart Association class III or IV heart failure

               -  History of myocardial infarction within the past 6 months

               -  Uncontrolled angina or electrocardiographic (ECG) evidence of acute ischemia

               -  Severe uncontrolled ventricular arrhythmias or ECG evidence of active conduction
                  system abnormalities

               -  Cardiac amyloidosis with hypotension (i.e., systolic blood pressure < 100 mm Hg)

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent study compliance or completion of study treatment

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Prior high-dose corticosteroid therapy for 12 days or less is permitted for emergent
             complications from newly diagnosed multiple myeloma

          -  More than 14 days since prior investigational agents

          -  No concurrent steroids or any other anticancer agents or treatments

             - Patients may receive the equivalent of up to 20 mg prednisone per day for concurrent
             illness or adrenal replacement therapy

          -  Concurrent palliative radiotherapy for bony pain or fracture is allowed