A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib
Intervention description: Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: multiple myeloma; myeloma; relapsed myeloma; refractory myeloma; relapsed, refractory myeloma; relapsed, refractory multiple myeloma; refractory multiple myeloma; relapsed multiple myeloma; B lymphoid malignancies; Myeloma, Plasma-Cell; Myeloma Proteins; hnRNP A1; myeloma helix-destabilizing protein, mouse; IgC3kappa Jir protein, human; gamma 3 myeloma protein Jir, human; M-proteins (Myeloma); M315 myeloma protein, mouse; myeloma protein M 315, mouse; McPC603 antibody; myeloma protein McPC603 antibody; multiple myeloma M-proteins; M protein, multiple myeloma; myeloma cell activator; myeloma immunoglobulins; myeloma immunoglobulin M603; myeloma immunoglobulin S15; myeloma protein A48, mouse; A48 myeloma protein, mouse; ABPC48 myeloma protein, mouse; myeloma protein A 48, mouse; myeloma protein Dob; myeloma protein M 467; myeloma protein M467; myeloma protein MOPC 141, mouse; MOPC141 myeloma protein, mouse; myeloma protein MOPC 173; myeloma protein Rou; IgA2 myeloma protein Rou; myeloma protein TEPC15; myeloma protein T15; myeloma protein TEPC 15; myeloma protein W3129; myeloma protein WIE; myeloma-associated membrane antigen KMA; myeloma antigen KMA; MYEOV protein, human; protein 460; myeloma protein MOPC 460; TRAPPC1 protein, human; multiple myeloma protein 2, human; Wis heavy-chain disease protein, human; myeloma protein Wis, human

Summary:

      The purpose of this study is to determine whether the combination of bevacizumab and
      bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have been previously diagnosed with multiple myeloma based on Durie-Salmon
             criteria and/or the diagnostic criteria developed by the International Myeloma Working
             Group (IMWG).The patient must currently require therapy for relapsed (progressive
             disease, defined as a 25% increase in M-protein, development of new or worsening of
             existing lesions or soft tissue plasmacytoma, or hypercalcemia, or relapse from CR. Or
             patient must have disease that is refractory to most recent therapy. Defined as less
             than a 50% reduction in serum paraprotein or 90% reduction in urine paraprotein.

          -  Must have measurable disease, defined as follows: For secretory multiple myeloma,
             measurable levels of monoclonal protein: greater than or equal to 0.5g/dL on
             electrophoresis or greater than or equal to 200mg of monoclonal light chain on a 24
             hour protein electrophoresis.

          -  Must have had at least one prior line of therapy but no more than three prior lines of
             therapy.

          -  Must understand and voluntarily sign an informed consent form.

          -  Must be greater than/equal to 18 years of age at time of signing consent.

          -  Must be able to adhere to study visit schedule and other protocol requirements.

          -  Must have an ECOG performance status of 0,1or 2

          -  Women of Child-bearing potential (WCBP) defined as a sexually mature woman who has not
             undergone a hysterectomy or who has not been naturally post-menopausal for at least 24
             consecutive months must have a negative serum or urine pregnancy test within 7 days of
             starting study drug. In addition, sexually active WCBP must agree to use adequate
             contraceptive methods (oral, injectable, or implantable hormonal contraceptive method;
             tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or
             vasectomized partner) while on study medication.

          -  All WCBP and all sexually active male patients must agree to use adequate methods of
             birth control throughout the study.

        Exclusion Criteria:

          -  Inability to comply with study and/or follow-up procedures

          -  Life expectancy of less than 12 weeks

          -  Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
             diastolic blood pressure > 100 mmHg on antihypertensive medications)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure or left
             ventricular ejection fraction (LVEF) < 40% (Note: baseline evaluation of LVEF should
             be performed for any patient who has received >450mg/m2 of any anthracycline during
             prior chemotherapy.

          -  History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Known CNS disease

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  Symptomatic peripheral vascular disease

          -  Known hypersensitivity to any component of bevacizumab and/or bortezomib

          -  Previously treated with Bortezomib and/or Bevacizumab.

          -  Received nitrosoureas within 3 weeks or any other chemotherapy, including thalidomide
             or clarithromycin, or radiation therapy before enrollment.

          -  Received corticosteroids (greater than 10mg/day prednisone or equivalent) within three
             weeks prior to enrollment.

          -  Received immunotherapy or antibody therapy within 8 weeks prior to enrollment.

          -  Received plasmapheresis within 4 weeks before enrollment.

          -  Had major surgery within 4 weeks before enrollment. (kyphoplasty is not considered
             major surgery)

          -  History of allergic reactions attributable to compounds containing boron or mannitol.

          -  Grade 3 or greater peripheral neuropathy as defined by the NCI Common Toxicity
             Criteria (NCI CTC version 3.0) Grade 3: Sensory loss or paresthesia interfering with
             ADLs. Grade 4: Permanent sensory loss that interferes with function.