Safety and Efficacy Study of Single Weekly Bortezomib in Newly Diagnosed Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib
Intervention description: Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle.
Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Bortezomib; Newly diagnosed; Newly diagnosed Multiple Myeloma

Summary:

      This is a research study to see if a new drug called bortezomib is useful to treat multiple
      myeloma in people who are newly diagnosed, and have not yet received treatment for their
      disease. VELCADE® (bortezomib) for Injection is a drug under development by Millennium
      Pharmaceuticals, Inc.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of multiple myeloma based on standard criteria.

          2. Measurable disease, defined as a monoclonal immunoglobulin spike on serum
             electrophoresis of > 1Gm/dL and/or urine monoclonal immunoglobulin spike of > 200mg/24
             hours.

          3. Non-secretors must have measurable protein by Freelite or measurable disease such as
             plasmacytoma to be eligible.

          4. Patient must not have been previously treated with chemotherapy. Prior treatment of
             hypercalcemia with corticosteroids, or bisphosphonates does not disqualify the
             patient.

          5. Patient must be ineligible for autologous stem cell transplant due to one or more of
             the following reasons:

               -  Age>65

               -  Impaired renal function (creatinine≥2.0 mg/dL)

               -  Impaired pulmonary function (DLCO≤50%)

               -  Poor performance status (KPS≤80)

               -  Other prohibitive comorbid disorder

                    -  5b. Patients≥60 who decline autologous stem cell transplant are eligible for
                       this study.

                    -  5c. Patients who are eligible but wish to postpone autologous stem cell
                       transplant are eligible for this study.

          6. Karnofsky performance status>50

          7. Patients treated with local radiotherapy with or without a brief exposure to steroids
             are eligible. Patients who require concurrent radiotherapy should have entry to the
             protocol deferred until the radiotherapy is completed, followed by a four week wash
             out period Spot RT to ≤3 vertebrae acceptable prior to entry.

          8. Meets the following pretreatment laboratory criteria at Baseline (Within 14 days prior
             to study drug administration):

               1. Platelet count>50x10^9/L or, if the bone marrow is extensively
                  infiltrated,>30x10^9/L

               2. Hemoglobin>8.0G/dL

               3. Absolute neutrophil count >1.0x10^9/L or, if the bone marrow is extensively
                  infiltrated, >0.5x10^9/L

          9. Meets the following pretreatment laboratory criteria for liver function tests at the
             screening visit conducted within 14 days of registration

               1. AST (SGOT): <3 times the upper limit of institutional laboratory normal

               2. ALT (SGPT): <3 times the upper limit of institutional laboratory normal

               3. Total bilirubin: <2 times the upper limit of institutional laboratory normal,
                  unless clearly related to the disease

         10. Women with child-bearing potential should be practicing an adequate form of
             contraception, as judged by the investigator (i.e. birth control pills, double barrier
             method, abstinence, etc.) or be surgically sterile or 12 months post-menopausal. Male
             subject agrees to use an acceptable method for contraception for the duration of the
             study.

         11. Age 18 years or older

         12. Has given voluntary written informed consent.

        Exclusion Criteria:

          1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein (M-protein) and skin changes)

          2. Plasma cell leukemia

          3. Impaired kidney function requiring dialysis, patients on hemodialysis are excluded

          4. Receiving steroids >the equivalent of 10mg prednisone daily for other medical
             conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis

          5. Infection not controlled by antibiotics

          6. HIV infection. Patients should provide consent for HIV testing according to the
             institution's standard practice

          7. Known active hepatitis B or C

          8. Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure (Appendix D), uncontrolled angina,
             severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities

          9. Second malignancy requiring concurrent treatment

         10. Other serious medical or psychiatric illness that could potentially interfere with the
             completion of treatment according to this protocol

         11. Positive pregnancy test in women of childbearing potential

         12. Patient has hypersensitivity to boron or mannitol.

         13. Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.

         14. Patient has received other investigational drugs with 14 days before enrollment