Multiple myeloma, relapsed/refractory after at least 2 lines of prior therapy
Conditions
Interventions
Product Name: Bevacizumab
Product Code: RO4876646
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentr
Sponsors
Roche Austria GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of multiple myeloma with evaluable disease parameters. Measurable secretory disease defined as either: - Quantifiable serum monoclonal immunoglobulin > 1 g/dl for IgG, > 0.5 g/dl for IgA or > 0.05 g/dl for IgD - Measurable urine levels of Bence-Jones protein (> 200mg/24 hours) 2. Progressive disease after 2 lines of prior therapy: This includes progressive disease after an initial response (complete, partial or minimal) to a salvage regimen or progression during such therapy. A single line of therapy may consist of one or more cytotoxic/biological agents such as melphalan plus prednisone; vincristine plus adriamycin plus dexamethasone (VAD); pulsed high-dose dexamethasone; thalidomide + dexamethasone; bortezomib. A single line of therapy is also defined as induction therapy (such as VAD) followed by high-dose melphalan with autologous stem cell transplantation plus maintenance treatment. Progressive disease as defined by one of the following criteria: - > 25% increase in M-protein - development of new or worsening lytic bone lesions - development of new or worsening plasmacytoma - development of new or worsening hypercalcemia despite appropriate medical treatment 3. Age 19 – 80 years. 4. ECOG performance status 0 or 1 or 2. 5. Life expectancy greater than 3 months. 6. At the time of screening, hematologic values within the following limits: - Absolute neutrophil count >/= 1’000/µl - Platelet count >/= 75’000/µl - Hemoglobin >/= 8.0 g/dl without transfusion support for 7 days 7. Adequate liver function: - AST/ALT /= 30 ml/min 9. Urinalysis: Urine dipstick of proteinuria 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24–hour urine collection and must demonstrate =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Non-secretory myeloma 2. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0 (Patients must have recovered from any major surgery), or anticipation of need for major surgical procedure during the course of the study. 3. Clinical or radiological evidence of CNS involvement or spinal cord compression. 4. Planned radiotherapy for underlying disease (prior completed radiotherapy treatment allowed). 5. Past or current history (within the last 5 years) of malignancies except for the indication under this study and curatively treated: - Basal and squamous cell carcinoma of the skin - In-situ carcinoma of the cervix 6 Serious non-healing wound, ulcer or bone fracture. 7. Evidence of any severe active acute or chronic infection. 8. Evidence of bleeding diathesis or coagulopathy. 9. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (= 6 months), myocardial infarction (= 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 10 Uncontrolled hypertension 11. Chronic, daily treatment with aspirin (>325mg/day) or clopidogrel (>75mg/day). 12. Treatment with any investigational drug or participation in another investigational study within 30 days prior to enrolment. 13. Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications 14. A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drug. 15. HIV-positive, Hbs-antigen positive or HCV-RNA-positive patients. 16. Pregnancy (positive serum pregnancy test) and lactation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the activity of Bevacizumab as measured by overall response (complete and partial response) in patients with relapsed/refractory multiple myeloma;Primary end point(s): complete and partial response rate;Secondary Objective: • To evaluate the safety of bevacizumab in this patient population • To evaluate the activity of bevacizumab on progression free survival and overall survival • To evaluate the activity of bevacizumab in multiple myeloma as measured by surrogate parameters of angiogenesis (bone marrow microvessel density, vascular endothelial growth factor expression by myeloma cells; serum levels of angiogenic cytokines) | — |
Countries
Austria
Outcome results
None listed