Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00171925
Recruitment Status : Terminated (Recruitment in study could not be reached after 8 yrs of recruiting)
First Posted : September 15, 2005
Results First Posted : April 20, 2011
Last Update Posted : April 11, 2012
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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 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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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.

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

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00171925

Novartis Investigative Site
Berlin, Germany
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals Identifier: NCT00171925     History of Changes
Other Study ID Numbers: CZOL446 DE01
First Posted: September 15, 2005    Key Record Dates
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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Vitamin D
Zoledronic acid
Calcium, Dietary
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents