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

NCT00972959 | Completed Phase 2 Results

• 1 other identifier: 26866138MMY 2051
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief 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

Conditions

Multiple Myeloma

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

Outcome Measures

Primary Outcomes (1)

• Bone Mineral Density (BMD)

  BMD of the lumbar spine (L1-L4, anteroposterior view) and femoral neck (FN) was measured by dual energy X-ray absorptiometry (DXA) using a Hologic QDR-1000 scanner on day 21 of cycle 4 (day 84)

  day 84

Secondary Outcomes (11)

• Bone Mineral Density (BMD)

  day 168

• Bone Remodelling

  day 84

• Bone Remodelling

  day 168

• Bone Pain

  On the day 84

• Bone Pain

  On the day 168

Study Arms (1)

Bortezomib/Dexamethasone/Zoledronic Acid

EXPERIMENTAL

For this study, Velcade will be administered at the standard dose of 1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle. Dexamethasone will be administered at a dose of 12 mg/m2 p.o., on days 1-2, 4-5, 8-9 and 11-12 of the same cycle. Zoledronic acid will be administered at a dose of 4 mg, iv (15-minute infusion), every 28 days for up to 8 cycles, and then every 28 days for the next 18 months

Drug: Bortezomib; Drug: Zoledronic Acid; Drug: Dexamethasone

Interventions

Bortezomib DRUG

1.3 mg/m2, iv, bolus, on days 1, 4, 8 and 11 of a 21-day cycle for up to 8 chemotherapy cycles

Also known as: Velcade

Bortezomib/Dexamethasone/Zoledronic Acid

Zoledronic Acid DRUG

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

Also known as: Zometa

Bortezomib/Dexamethasone/Zoledronic Acid

Dexamethasone DRUG

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

Bortezomib/Dexamethasone/Zoledronic Acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Athens: lead

Study Sites (3)

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

Athens, 115 28, Greece

Location

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

Athens, 11525, Greece

Location

Department of Hematology, "Theagenion" Cancer Center

Thessaloniki, 540 07, Greece

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Zoledronic Acid; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Azoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Prof. M. A. Dimopoulos
• Organization: Department of Clinical Therapeutics, University of Athens School of Medicine, "Alexandra" General Hospital of Athens,

mdimop@med.uoa.gr

0030 210 3381511

Study Officials

• Meletios- Athanasios Dimopoulos, Professor

  Therapeutic Clinic Department, Faculty of Medicine. University of Athens

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the clinic

Study Record Dates

• First Submitted: September 8, 2009
• First Posted: September 9, 2009
• Study Start: July 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: August 5, 2014
• Results First Posted: August 5, 2014

Record last verified: 2014-07

Locations

GR (3)