Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I

Multiple myeloma is a disease of B-lymphocytes producing malignant plasma cells. Malignant plasma cells induce osteolytic lesions, which is characteristic for progression of multiple myeloma. It is the aim of this study to investigate whether zoledronic acid has an influence on the progression of multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma Stage I
• Intervention / Treatment: Drug: Zoledronic acid; Dietary supplement: Calcium / Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Evidence of myeloma according to the criteria of the British Columbia Cancer Agency (for the diagnosis, 2 of the 3 criteria must be met):

  • Evidence of paraprotein in the serum or urine
  • Bone marrow infiltration with plasma cells which represent more than 10% of the nucleated cells
  • Radiologically, at least one osteolytic lesion
• Asymptomatic patients with Stage I (Durie and Salmon) multiple myeloma

Exclusion criteria:

• Patients with more than one osteolytic lesion on conventional skeletal radiography
• Previous treatment with bisphosphonates
• bilirubin > 2.5 mg/dl

• Abnormal renal function as evidenced by: A calculated creatinine clearance < 30 ml/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula:

  • CrCl= [140-age(years)] x weight(kg)/[72xserumcreatinine(mg/dL)] X {0.85 for female patients}
• Patients with other malignant diseases or severe concomitant diseases
• Potentially fertile patients who are not using a reliable and appropriate method of contraception
• Pregnancy or breast-feeding
• Participation in another clinical study with an investigational drug within 12 weeks of study entry
• Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)

Other protocol-defined inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zoledronic acid (ZOL446); Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.	Drug: Zoledronic acid; Zoledronic acid administered via normal saline intravenous infusion (over 15 minutes) every 4 weeks. Dosage was according to calculated creatinine clearance: patients with baseline creatinine clearance > 60 ml/min received 4 mg; for patients with mild to moderate renal impairment, doses were calculated to achieve the same AUC as that achieved in patients with creatinine clearance of 75 ml/min, assuming target AUC of 0.66 (mg*hr/l).; Dietary supplement: Calcium / Vitamin D; Patients on zoledronic acid received 500 mg calcium and 400-500 IU vitamin D combination tablet daily.
No Intervention: Control; No treatment with study medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days of Progression Free Survival	Progression-free survival was defined as time from date of randomization to death from any cause or one of the following events: progression to stage II or III according to Salmon & Durie classification; skeletal related events (pathologic fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or hypercalcemia); unequivocal progression of osteolytic lesions (at least a 20% increase in the largest diameter of one existing osteolytic lesion which is measured in at least one dimension as 20 mm with conventional techniques), determined radiologically.	48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Progression by Individual Criteria	Number of patients with progression by individual criteria consisting of Progression of disease overall, Skeletal-related events (including pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression or Hypercalcemia), Progression to stage II or III according to Salmon & Durie classification, and unequivocal progression of osteolytic lesion. Patients are counted separately for every type of progression, but only once for Overall Progression.	48 months
The Number of Participants With the Development of Skeletal Complications	Pathologic fracture: bone fractures that occur spontaneously or from trivial trauma. New vertebral compression fracture defined as a decrease in vertebral height of 25% from baseline; Spinal cord compression: the impingement of tumor on the spinal cord confirmed by radiography; Bone Radiotherapy: Bone irradiation to palliate painful lesions, treat or prevent pathologic fractures or spinal cord compression; Surgery on bone: surgical procedures performed to set, stabilize or prevent pathologic fractures or areas of spinal cord compression; Hypercalcemia: Corrected serum calcium ≥ 12.0 mg/dl	48 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2000
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): April 11, 2012
• Last Update Submitted That Met QC Criteria: April 5, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Progression; Multiple Myeloma; Stage I; Zoledronic acid
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Zoledronic Acid
• Other Study ID Numbers: CZOL446 DE01