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Effect of Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Disease in Patients With Multiple Myeloma Relapsed After 1-3 Prior Lines of Therapy

Information source: University of Athens
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Multiple Myeloma

Intervention: Bortezomib (Drug); Zoledronic Acid (Drug); Dexamethasone (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: University of Athens

Official(s) and/or principal investigator(s):
Meletios- Athanasios Dimopoulos, Professor, Study Chair, Affiliation: Therapeutic Clinic Department, Faculty of Medicine. University of Athens

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

Clinical Details

Official title: A Prospective, Multicenter, Non-comparative, Open-label, Phase II Study to Evaluate the Effects of the Combination of Bortezomib/Dexamethasone/Zoledronic Acid on Bone Mineral Density, Bone Metabolism, Radiographically-detected Osteolytic Bone Lesions, Skeletal-related Events and Bone Pain in Patients With Multiple Myeloma Who Have Relapsed After 1-3 Prior Lines of Therapy

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Bone Mineral Density (BMD)

Secondary outcome:

Bone Mineral Density (BMD)

Bone Remodelling

Bone Remodelling

Bone Pain

Bone Pain

Skeletal Survey for New Osteolytic Lesions/Fractures

Skeletal Survey for New Osteolytic Lesions/Fractures

New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)

New Skeletal-related Events (SRE: Pathologic Fractures, Need for Bone Radiation Therapy or Surgery)

Bone Remodelling

Bone Remodelling

Detailed description: Multiple Myeloma represents a malignant proliferation of plasma cells derived from a single clone. The most common symptom in myeloma, affecting more than 70% of patients at diagnosis, is bone pain. The pain usually involves the back and ribs, and is precipitated by movement. Bone fractures are commonly seen in myeloma patients and may present with persistent localized pain. VELCADE (bortezomib) is a proteasome inhibitor used for the treatment of multiple myeloma. VELCADE seems to be the first agent to combine significant anti-myeloma activity and beneficial effects on bone remodeling. Thus, it appears to be a very promising tool for the treatment of myeloma patients. In this study, a regimen consisting of bortezomib/dexamethasone/zoledronic acid will be used. The rationale for using this regimen is that:

- VELCADE (bortezomib) is indicated for the treatment of relapsed myeloma patients

participating in the study and it has also a beneficial effect on biochemical markers of bone formation.

- In phase II studies, the addition of dexamethasone in patients with a suboptimal

response to bortezomib alone improved efficacy in relapsed or refractory multiple myeloma patients, without increasing adverse events. Therefore, in this study, the addition of dexamethasone aims at providing the optimal therapy for participating myeloma patients.

- Zoledronic acid, the most potent i. v. bisphosphonate, is used because of its

established effect on reducing skeletal related events in patients with multiple myeloma due to its inhibitory effect on osteoclastic bone resorption. Dosages and timing of dosages are based on current recommendations and guidelines for the treatment of myeloma patients who Have Relapsed after 1-3 Prior Lines of Therapy.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

Department of Clinical Therapeutics, University of Athens School of Medicine, "Alexandra" General Hospital, Athens 115 28, Greece

Department of Hematology & Medical Research, 251 General Air Force Hospital, Athens 11525, Greece

Department of Hematology, "Theagenion" Cancer Center, Thessaloniki 540 07, Greece

Additional Information

Starting date: July 2009
Last updated: July 8, 2014

Page last updated: August 23, 2015

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