Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I

This study has been terminated.
(Recruitment in study could not be reached after 8 yrs of recruiting)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00171925
First received: September 13, 2005
Last updated: April 5, 2012
Last verified: April 2012
  Purpose

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 Intervention Phase
Multiple Myeloma Stage I
Drug: Zoledronic acid
Dietary Supplement: Calcium / Vitamin D
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Days of Progression Free Survival [ Time Frame: 48 months ] [ Designated as safety issue: No ]

    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:
  • Number of Patients With Progression by Individual Criteria [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    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.

  • The Number of Participants With the Development of Skeletal Complications [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    • 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


Enrollment: 143
Study Start Date: August 2000
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00171925

Locations
Germany
Novartis Investigative Site
Berlin, Germany
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00171925     History of Changes
Other Study ID Numbers: CZOL446 DE01
Study First Received: September 13, 2005
Results First Received: January 20, 2011
Last Updated: April 5, 2012
Health Authority: United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Multiple Myeloma
Stage I
Zoledronic acid
Progression

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

ClinicalTrials.gov processed this record on October 23, 2014