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Recruitment in study could not be reached after 8 yrs of recruiting
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zoledronic acid (ZOL446) | Experimental | Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily. |
|
| Control | No Intervention | No treatment with study medication. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zoledronic acid | Drug | 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). |
| 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:
| 48 months |
| 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. |
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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):
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Berlin | Germany |
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| ID | Title | Description |
|---|---|---|
| FG000 | Zoledronic Acid (ZOL446) | Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily. |
| FG001 | Control | No Treatment with study medication. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Zoledronic Acid (ZOL446) | Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily. |
| BG001 | Control | No Treatment with study medication. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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:
| Intent to Treat Population | Posted | Mean | Standard Error | Days | 48 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Zoledronic Acid | Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 10.X | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 10.X | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D018450 | Disease Progression |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D000077211 | Zoledronic Acid |
| D002118 | Calcium |
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
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|
| Calcium / Vitamin D | Dietary Supplement | Patients on zoledronic acid received 500 mg calcium and 400-500 IU vitamin D combination tablet daily. |
|
| 48 months |
| The Number of Participants With the Development of Skeletal Complications |
| 48 months |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| Administrative problems |
|
| Death |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Control | No Treatment with study medication. |
|
|
| Secondary | 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. | Intent to Treat Population | Posted | Number | Participants | 48 months |
|
|
|
| Secondary | The Number of Participants With the Development of Skeletal Complications |
| Intent to treat population | Posted | Number | Participants | 48 months |
|
|
|
| 28 |
| 72 |
| 61 |
| 72 |
| EG001 | Control | No treatment with study medication. | 12 | 71 | 51 | 71 |
| Aortic valve disease | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
|
| Cardiac amyloidosis | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
|
| Cardiac disorder | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
|
| Left ventricular failure | Cardiac disorders | MedDRA 10.X | Systematic Assessment |
|
| Phimosis | Congenital, familial and genetic disorders | MedDRA 10.X | Systematic Assessment |
|
| Goitre | Endocrine disorders | MedDRA 10.X | Systematic Assessment |
|
| Toxic nodular goitre | Endocrine disorders | MedDRA 10.X | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Condition aggravated | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Death | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Multi-organ failure | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA 10.X | Systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA 10.X | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Haematoma infection | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Jaw fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Open wound | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Traumatic brain injury | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA 10.X | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA 10.X | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 10.X | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 10.X | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 10.X | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Arthritis reactive | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Osteonecrosis of the jaw | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
|
| Meningioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
|
| Multiple myeloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
|
| Papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
|
| Small cell lung cancer stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 10.X | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Polyneuropathy | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Radicular syndrome | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Stupor | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Alcohol withdrawal syndrome | Psychiatric disorders | MedDRA 10.X | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 10.X | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 10.X | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 10.X | Systematic Assessment |
|
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 10.X | Systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA 10.X | Systematic Assessment |
|
| Uterine malposition | Reproductive system and breast disorders | MedDRA 10.X | Systematic Assessment |
|
| Bronchitis chronic | Respiratory, thoracic and mediastinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 10.X | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Chills | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Pain | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 10.X | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 10.X | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 10.X | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.X | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 10.X | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 10.X | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 10.X | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 10.X | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007093 |
| Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D008673 | Metals, Alkaline Earth |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D008670 | Metals |
| D001779 | Blood Coagulation Factors |
| D001685 | Biological Factors |
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| Progression to stage II or III |
|
| Unequivocal progression of osteolytic lesion |
|
| Initiation of radiotherapy or surgery on bone |
|
| Spinal cord compression |
|
| Hypercalcemia |
|