Bevacizumab, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Stage II or III Multiple Myeloma
Condition: Multiple Myeloma in Relapse; Stage II Multiple Myeloma; Stage III Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: bevacizumab; lenalidomide; dexamethasone
Intervention description: Given IV; Given orally; Given orally
Intervention MeSH terms: Dexamethasone; Bevacizumab; Antineoplastic Agents, Immunological; Lenalidomide; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with lenalidomide and
      dexamethasone works in treating patients with relapsed or refractory stage II or stage III
      multiple myeloma. Monoclonal antibodies, such as bevacizumab, can block cancer growth in
      different ways. Some block the ability of cancer cells to grow and spread. Others find cancer
      cells and help kill them or carry cancer-killing substances to them. Bevacizumab and
      lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer.
      Dexamethasone may stimulate the immune system in different ways and stop cancer cells from
      growing. Giving bevacizumab together with lenalidomide and dexamethasone may kill more cancer
      cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed symptomatic multiple myeloma:

               -  Stage II or III disease

               -  Relapsed or refractory disease after >= 2 courses of prior chemotherapy

          -  Measurable levels of monoclonal protein (M protein) > 1.0 g/dL by serum protein
             electrophoresis OR > 200 mg of monoclonal light chain by 24-hour urine protein
             electrophoresis

          -  Measurable bone disease, defined as >= 1 unidimensionally measurable lesion (longest
             diameter to be recorded) >= 20 mm with conventional techniques OR >= 10 mm with spiral
             CT scan (for patients with lytic bone disease)

          -  No known brain metastases

          -  ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100%

               -  Patients with PS of 3 are eligible if it is due to pain that is likely to improve
                  with treatment

          -  Life expectancy > 6 months

          -  No known HIV positivity

          -  No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
             the past 6 months

          -  No active infections requiring oral or intravenous antibiotics within the past week

          -  No proteinuria (i.e., albuminuria) > 1,000 mg/24 hours unless related to the diagnosis
             of multiple myeloma

               -  Patients with light chain (i.e., "Bence-Jones") proteinuria are still eligible if
                  the non-light chain component of protein is < 1,000 mg/24 hours

          -  No serious nonhealing wound or ulcer

          -  No blood pressure > 150/90 mm Hg (even with medication)

          -  No significant traumatic injury within the past 28 days

          -  No clinically significant peripheral vascular disease

          -  No evidence of bleeding diathesis or coagulopathy

          -  No unstable angina or myocardial infarction within the past 6 months

          -  No stroke within the past 6 months

          -  No New York Heart Association class III or IV heart failure

          -  No secondary malignancy within the past 2 years except squamous cell or basal cell
             carcinoma of the skin or carcinoma in situ of the cervix

          -  Hemoglobin > 9 g/dL (may be supported by transfusion or growth factors)

          -  WBC >= 2,000/mm^3

          -  Absolute neutrophil count >= 1,000/mm^3

          -  Platelet count >= 75,000/mm^3

          -  Bilirubin =< 2.5 mg/dL

          -  At least 4 weeks since prior chemotherapy or radiotherapy and recovered

          -  More than 7 days since prior minor surgical procedures, fine-needle aspirations, or
             core biopsies:

        More than 24 hours since prior bone marrow biopsy or central veinous access placement

          -  More than 28 days since prior major surgical procedure or open biopsy

          -  At least 4 weeks since prior and no concurrent participation in another experimental
             drug study

          -  Prior autologous peripheral blood stem cell transplantation allowed

          -  No prior lenalidomide

          -  Concurrent full-dose anticoagulants allowed provided all of the following criteria are
             met:

               -  No active bleeding or pathological condition that carries a high risk of bleeding
                  (e.g., tumor involving major vessels or known varices)

               -  No thrombocytopenia requiring transfusion

               -  Platelet count > 75,000/mm3

               -  INR 2-3 and stable

          -  No concurrent major surgery

          -  No concurrent sargramostim (GM-CSF)

          -  No other concurrent investigational agents

          -  No other concurrent anticancer agents or therapies

          -  AST and ALT =< 5 times upper limit of normal

          -  Creatinine < 2.5 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use 2 methods of effective contraception 4 weeks before, during,
             and 4 weeks after completion of study treatment

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to lenalidomide and/or bevacizumab or other agents used in the
             study