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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Multiple Myeloma

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Bone Mineral Density (BMD)

Outcome Description:

At the end of cycle 4 (day 84) from the treatment initiation

Outcome Time Frame:

day 84

Safety Issue:

No

Principal Investigator

Meletios- Athanasios Dimopoulos, Professor

Investigator Role:

Study Chair

Investigator Affiliation:

Therapeutic Clinic Department, Faculty of Medicine. University of Athens

Authority:

Greece: National Organization of Medicines

Study ID:

26866138MMY 2051

NCT ID:

NCT00972959

Start Date:

July 2009

Completion Date:

December 2014

Related Keywords:

  • Multiple Myeloma
  • 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
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

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