Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Bortezomib; Zoledronic Acid; Dexamethasone
Intervention description: 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle for up to 8 chemotherapy cycles; 4 mg, iv, at a 15 min infusion, Day 1 of every cycle for up to 8 cycles, and then every 28 days for the next 18 months; 12 mg/m2 p.o. on days 1-2, 4-5, 8-9 and 11-12 of a 21-day cycle for up to 8 chemotherapy cycles
Intervention MeSH terms: Zoledronic Acid; Dexamethasone; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: multiple myeloma; 1-3 Prior Lines of Therapy; bortezomib (Velcade); zoledronic acid (Zometa); Dexamethasone; bone mineral density; bone pain; bone metabolism; osteolytic lesions; DEXA-scans; X-ray radiography

Summary:

      The aim of this study is to evaluate the effect of bortezomib in combination with
      dexamethasone and zoledronic acid on bone mineral density (BMD) and skeletal related events
      (SREs) in Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with Multiple Myeloma who Have Relapsed after 1-3 Prior Lines of Therapy

          -  Women > 50 years old

          -  Κarnofsky performance status ≥ 60 (patients with lower performance status due to
             myeloma bone disease can also be included)

          -  Measurable disease

          -  Platelet count >50x10(9)/L

          -  Neutrophil count >0.75x10(9)/L

          -  Hemoglobin ≥7.0 g/dL (the use of recombinant human erythropoietin or red blood Hell
             transfusions to maintain hemoglobin levels above 7.0 g/dL is not an exclusion
             criterion)

          -  Serum ALT and AST ≤ 3-fold of upper normal limit

          -  Serum bilirubin ≤ 2-fold of upper normal limit

          -  Serum Calcium ≤ 10.5 mg/dL

          -  Expected survival ≥ 2 months

          -  Signed informed consent

        Exclusion Criteria:

          -  Presence of another cancer

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study

          -  Grade 2-4 peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by
             NCI CTCAE version 3

          -  Pregnant women > 50 years old or breast-feeding

          -  Woman > 50 years old capable of becoming pregnant [anyone who has not undergone a
             hysterectomy, has not had both ovaries removed or has not been post-menopausal for
             more than 24 months in a row not using adequate contraception

          -  Known or suspected hypersensitivity or intolerance to bortezomib, boron, mannitol,
             zoledronic acid, dexamethasone, or heparin (if an indwelling catheter is used)

          -  Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable
             dose for at least 3 months prior to first dose of study drug)

          -  Uncontrolled or severe cardiovascular disease including myocardial infarction within 6
             months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure
             (Attachment 4, NYHA Classification of Cardiac Disease), uncontrolled angina,
             pericardial disease, or cardiac amyloidosis

          -  Acute diffuse infiltrative pulmonary disease

          -  History of hypotension or patient has decreased blood pressure (sitting systolic blood
             pressure [SBP] 100 mmHg and/or sitting diastolic blood pressure [DBP] 60 mmHg)

          -  Patient has received extensive radiation therapy, systemic chemotherapy, or other
             antineoplastic therapy within 4 weeks prior to enrolment

          -  Patient has received any drugs or agents that inhibit (e.g., cimetidine, erythromycin,
             fluoxetine, ketoconazole, paroxetine) or induce (e.g., carbamazepine, glucocorticoids,
             phenobarbital, rifampin) CYP2C19 or CYP3A4 within 14 days before the first dose of
             VELCADE (proton pump inhibitors are allowed)

          -  Need for therapy with concomitant CYP 3A4 inhibitors (e.g., itraconazole, fluconazole,
             clarithromycin, erythromycin, norfloxacin, fluvoxamine, cimetidine, indinavir,
             ritonavir) or inducers (e.g., efavirenz, barbiturates, phenytoin, rifampin,
             glitazones). Proton pump inhibitors are allowed.

          -  Patient has received an experimental drug or has used an experimental medical device
             within 4 weeks prior to the planned start of treatment. Concurrent participation in
             non-treatment studies is allowed, provided it will not interfere with participation in
             this study.