Study of Velcade® and Bone Formation in Patients With Relapsed/Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: VELCADE™
Intervention description: Patients will receive two cycles of VELCADE™ (1.3 mg/m2, 1.0 mg/m2 or 0.7 mg/m2) on days 1, 4, 8, and 11, on a 21 day cycle. No growth factors or bisphosphonates will be allowed during study treatment. Bone markers will be measured:
Days 1, 4, 8, 11: Pre-dose, post-dose, and every 2-4 hours for 8 hours Days 2-3, 5-7, 9-10, 12-21: every 24 hours, beginning with the immediate post-dose sample (+/- 2 hours) Other laboratory and radiologic studies will be performed as detailed in the Study Calendar.
Patients will complete the study after two cycles of VELCADE™. However, if a patient continues to receive VELCADE™ as part of his/her treatment for relapsing MM, routine bone markers may be monitored for the duration of VELCADE™ treatment as clinically indicated.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma

Summary:

      Velcade (bortezomib, PS-341) has recently been approved by the Food and Drug Administration
      (FDA) for the treatment of multiple myeloma for patients who have received at least one prior
      therapy. Velcade is a unique compound developed by scientists at Millennium Pharmaceuticals,
      Inc. Velcade enters cells and affects the way they divide. Cancer cells are particularly
      sensitive. Velcade interferes with the enzyme "proteasome" which is responsible for allowing
      cells to divide. When cancer cells cannot divide, they die. Velcade falls into the class of
      drugs known as "proteasome inhibitors."
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of histologically documented MM with relapsed or progressive disease after at
             least one line of prior therapy.

          -  Patient has measurable disease in which to capture response, defined as one or more of
             the following:

               -  Serum M-protein level > 1.0 gm/dl (10.0 g/L) measured by serum protein
                  electrophoresis or immunoglobulin electrophoresis; or

               -  Urinary M-protein excretion > 1000 mg/24 hours; or

               -  Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or

               -  Serum free light chains (by the Freelite test) > 2 X the upper limit of normal,
                  in the absence of renal failure.

               -  Evidence of active disease by radiographic techniques

          -  Performance status (PS) of <= 2 as per Southwest Oncology Group scale, unless PS of
             3-4 based solely on bone pain.

          -  Patients must have a platelet count >= 50,000/mm3, and an absolute neutrophil count of
             at least 1,000/μl.

          -  Patients must have adequate renal function defined as creatinine clearance > 30ml/min.

          -  Patients must have adequate hepatic function defined as serum transaminases and direct
             bilirubin < 2 X the upper limit of normal.

          -  Pregnant or nursing women may not participate. Women of childbearing potential must
             have a negative pregnancy test documented within one week of registration. Women of
             reproductive potential may not participate unless they have agreed to use an effective
             contraceptive method.

          -  Male or female adults of at least 18 years of age.

          -  Patients must have signed and Institutional Review Board approved written informed
             consent form and demonstrate willingness to meet follow-up schedule and study
             procedure obligations

        Exclusion Criteria:

          -  Chemotherapy or radiotherapy received within the previous 4 weeks.

          -  Has received previous bortezomib therapy

          -  Significant neurotoxicity, defined as grade > 2 neurotoxicity per National Cancer
             Institute Common Toxicity Criteria.

          -  Platelet count < 50,000/mm3, or ANC < 1,000/μl

          -  Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
             syndrome.

          -  Patient has hypersensitivity to bortezomib, boron, or mannitol

          -  Clinically significant hepatic dysfunction as noted by bilirubin or AST >3 times the
             upper normal limit or clinically significant concurrent hepatitis.

          -  New York Hospital Association Class III or Class IV heart failure.

          -  Myocardial infarction within the last 6 months.

          -  Non-secretory multiple myeloma, unless the patient has measurable lesions on computed
             tomography, magnetic resonance imaging and/or positron emission tomography.

          -  Uncontrolled, active infection.

          -  Patients with a history of treatment for clinically significant ventricular cardiac
             arrhythmias.

          -  Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric
             illness that could potentially interfere with the completion of treatment according to
             this protocol.

          -  Pregnant or potential for pregnancy. Women of childbearing potential will have a
             pregnancy [beta-HCG] test at screening, and will be required to use a medically
             approved contraceptive method. Pregnancy testing will be performed prior to
             administration of each cycle of study drug.

          -  Breast-feeding women may not participate.