NCT00171925

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
143

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Aug 2000

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2000

Completed
5.1 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 15, 2005

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2008

Completed
2.5 years until next milestone

Results Posted

Study results publicly available

April 20, 2011

Completed
Last Updated

April 11, 2012

Status Verified

April 1, 2012

Enrollment Period

8.3 years

First QC Date

September 13, 2005

Results QC Date

January 20, 2011

Last Update Submit

April 5, 2012

Conditions

Keywords

Multiple MyelomaStage IZoledronic acidProgression

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (2)

  • Number of Patients With Progression by Individual Criteria

    48 months

  • The Number of Participants With the Development of Skeletal Complications

    48 months

Study Arms (2)

Zoledronic acid (ZOL446)

EXPERIMENTAL

Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.

Drug: Zoledronic acidDietary Supplement: Calcium / Vitamin D

Control

NO INTERVENTION

No treatment with study medication.

Interventions

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).

Zoledronic acid (ZOL446)
Calcium / Vitamin DDIETARY_SUPPLEMENT

Patients on zoledronic acid received 500 mg calcium and 400-500 IU vitamin D combination tablet daily.

Zoledronic acid (ZOL446)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Novartis Investigative Site

Berlin, Germany

Location

MeSH Terms

Conditions

Multiple MyelomaDisease Progression

Interventions

Zoledronic AcidCalciumVitamin D

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsMetals, Alkaline EarthElementsInorganic ChemicalsMetalsBlood Coagulation FactorsBiological FactorsSecosteroidsSteroidsFused-Ring CompoundsPolycyclic Compounds

Limitations and Caveats

Only exploratory analyses were performed as the trial was terminated early due to lack of obtaining the required sample size. Secondary Outcomes for Quality of Life and Bone Markers not posted due to sparse data.

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 15, 2005

Study Start

August 1, 2000

Primary Completion

November 1, 2008

Study Completion

November 1, 2008

Last Updated

April 11, 2012

Results First Posted

April 20, 2011

Record last verified: 2012-04

Locations