Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I

• ClinicalTrials.gov Identifier: NCT00171925
• Recruitment Status: Terminated
• First Posted: September 15, 2005
• Results First Posted: April 20, 2011
• Last Update Posted: April 11, 2012
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma Stage I	Drug: Zoledronic acid; Dietary Supplement: Calcium / Vitamin D	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I
• Study Start Date: August 2000
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: November 2008

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Days of Progression Free Survival [ Time Frame: 48 months ]

   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.

Secondary Outcome Measures :

1. Number of Patients With Progression by Individual Criteria [ Time Frame: 48 months ]
   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.
2. The Number of Participants With the Development of Skeletal Complications [ Time Frame: 48 months ]
   • 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Germany

Novartis Investigative Site

Berlin, Germany

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00171925
• Other Study ID Numbers: CZOL446 DE01
• First Posted: September 15, 2005
• Results First Posted: April 20, 2011
• Last Update Posted: April 11, 2012
• Last Verified: April 2012

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Multiple Myeloma; Stage I; Zoledronic acid; Progression

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Vitamin D; Zoledronic Acid; Calcium; Vitamins; Micronutrients; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Bone Density Conservation Agents