Trial Outcomes & Findings for Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I (NCT NCT00171925)
NCT ID: NCT00171925
Last Updated: 2012-04-11
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
143 participants
Primary outcome timeframe
48 months
Results posted on
2012-04-11
Participant Flow
Participant milestones
| Measure |
Zoledronic Acid (ZOL446)
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
No Treatment with study medication.
|
|---|---|---|
|
Overall Study
STARTED
|
72
|
71
|
|
Overall Study
COMPLETED
|
42
|
40
|
|
Overall Study
NOT COMPLETED
|
30
|
31
|
Reasons for withdrawal
| Measure |
Zoledronic Acid (ZOL446)
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
No Treatment with study medication.
|
|---|---|---|
|
Overall Study
Adverse Event
|
10
|
6
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
9
|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Administrative problems
|
10
|
11
|
|
Overall Study
Death
|
1
|
2
|
Baseline Characteristics
Therapy With Zoledronic Acid in Patients With Multiple Myeloma Stage I
Baseline characteristics by cohort
| Measure |
Zoledronic Acid (ZOL446)
n=72 Participants
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
n=71 Participants
No Treatment with study medication.
|
Total
n=143 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
58.8 years
STANDARD_DEVIATION 12.02 • n=99 Participants
|
62.1 years
STANDARD_DEVIATION 10.79 • n=107 Participants
|
60.4 years
STANDARD_DEVIATION 11.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
73 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=99 Participants
|
40 Participants
n=107 Participants
|
70 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
69 participants
n=99 Participants
|
70 participants
n=107 Participants
|
139 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Oriental
|
2 participants
n=99 Participants
|
0 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=99 Participants
|
1 participants
n=107 Participants
|
2 participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
72 participants
n=99 Participants
|
71 participants
n=107 Participants
|
143 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 48 monthsPopulation: Intent to Treat Population
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.
Outcome measures
| Measure |
Zoledronic Acid (ZOL446)
n=71 Participants
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
n=69 Participants
No Treatment with study medication.
|
|---|---|---|
|
Days of Progression Free Survival
|
1078.1 Days
Standard Error 59.53
|
992.80 Days
Standard Error 61.83
|
SECONDARY outcome
Timeframe: 48 monthsPopulation: Intent to Treat Population
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.
Outcome measures
| Measure |
Zoledronic Acid (ZOL446)
n=71 Participants
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
n=69 Participants
No Treatment with study medication.
|
|---|---|---|
|
Number of Patients With Progression by Individual Criteria
Progression of disease overall
|
19 Participants
|
26 Participants
|
|
Number of Patients With Progression by Individual Criteria
Skeletal-related events
|
0 Participants
|
4 Participants
|
|
Number of Patients With Progression by Individual Criteria
Progression to stage II or III
|
17 Participants
|
24 Participants
|
|
Number of Patients With Progression by Individual Criteria
Unequivocal progression of osteolytic lesion
|
3 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 48 monthsPopulation: Intent to treat population
* 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
Outcome measures
| Measure |
Zoledronic Acid (ZOL446)
n=71 Participants
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
n=69 Participants
No Treatment with study medication.
|
|---|---|---|
|
The Number of Participants With the Development of Skeletal Complications
Skeletal events overall
|
0 Participants
|
4 Participants
|
|
The Number of Participants With the Development of Skeletal Complications
Pathological fracture
|
0 Participants
|
1 Participants
|
|
The Number of Participants With the Development of Skeletal Complications
Initiation of radiotherapy or surgery on bone
|
0 Participants
|
1 Participants
|
|
The Number of Participants With the Development of Skeletal Complications
Spinal cord compression
|
0 Participants
|
2 Participants
|
|
The Number of Participants With the Development of Skeletal Complications
Hypercalcemia
|
0 Participants
|
0 Participants
|
Adverse Events
Zoledronic Acid
Serious events: 28 serious events
Other events: 61 other events
Deaths: 0 deaths
Control
Serious events: 12 serious events
Other events: 51 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zoledronic Acid
n=72 participants at risk
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
n=71 participants at risk
No treatment with study medication.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.4%
1/72
|
1.4%
1/71
|
|
Cardiac disorders
Aortic valve disease
|
1.4%
1/72
|
0.00%
0/71
|
|
Cardiac disorders
Arrhythmia
|
1.4%
1/72
|
0.00%
0/71
|
|
Cardiac disorders
Cardiac amyloidosis
|
1.4%
1/72
|
0.00%
0/71
|
|
Cardiac disorders
Cardiac disorder
|
0.00%
0/72
|
1.4%
1/71
|
|
Cardiac disorders
Left ventricular failure
|
1.4%
1/72
|
0.00%
0/71
|
|
Congenital, familial and genetic disorders
Phimosis
|
1.4%
1/72
|
0.00%
0/71
|
|
Endocrine disorders
Goitre
|
1.4%
1/72
|
0.00%
0/71
|
|
Endocrine disorders
Toxic nodular goitre
|
1.4%
1/72
|
0.00%
0/71
|
|
Gastrointestinal disorders
Abdominal pain
|
1.4%
1/72
|
0.00%
0/71
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/72
|
1.4%
1/71
|
|
General disorders
Condition aggravated
|
1.4%
1/72
|
0.00%
0/71
|
|
General disorders
Death
|
0.00%
0/72
|
1.4%
1/71
|
|
General disorders
Multi-organ failure
|
0.00%
0/72
|
1.4%
1/71
|
|
General disorders
Oedema
|
1.4%
1/72
|
0.00%
0/71
|
|
General disorders
Pyrexia
|
2.8%
2/72
|
0.00%
0/71
|
|
Hepatobiliary disorders
Cholecystitis
|
1.4%
1/72
|
0.00%
0/71
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.4%
1/72
|
1.4%
1/71
|
|
Infections and infestations
Erysipelas
|
1.4%
1/72
|
0.00%
0/71
|
|
Infections and infestations
Haematoma infection
|
1.4%
1/72
|
0.00%
0/71
|
|
Infections and infestations
Herpes zoster
|
1.4%
1/72
|
0.00%
0/71
|
|
Infections and infestations
Pneumonia
|
1.4%
1/72
|
1.4%
1/71
|
|
Infections and infestations
Sepsis
|
0.00%
0/72
|
1.4%
1/71
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Foot fracture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Head injury
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/72
|
1.4%
1/71
|
|
Injury, poisoning and procedural complications
Jaw fracture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Joint injury
|
2.8%
2/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Ligament rupture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
2.8%
2/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Open wound
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Rib fracture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Traumatic brain injury
|
1.4%
1/72
|
0.00%
0/71
|
|
Injury, poisoning and procedural complications
Wound
|
1.4%
1/72
|
0.00%
0/71
|
|
Investigations
Blood glucose increased
|
1.4%
1/72
|
0.00%
0/71
|
|
Investigations
Haemoglobin decreased
|
1.4%
1/72
|
0.00%
0/71
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/72
|
1.4%
1/71
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
1.4%
1/72
|
1.4%
1/71
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/72
|
1.4%
1/71
|
|
Musculoskeletal and connective tissue disorders
Arthritis reactive
|
1.4%
1/72
|
0.00%
0/71
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder
|
1.4%
1/72
|
0.00%
0/71
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
4.2%
3/72
|
0.00%
0/71
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis of the jaw
|
5.6%
4/72
|
0.00%
0/71
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
1.4%
1/72
|
0.00%
0/71
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Meningioma
|
0.00%
0/72
|
1.4%
1/71
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
0.00%
0/72
|
1.4%
1/71
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papilloma
|
1.4%
1/72
|
0.00%
0/71
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.00%
0/72
|
1.4%
1/71
|
|
Nervous system disorders
Dizziness
|
1.4%
1/72
|
0.00%
0/71
|
|
Nervous system disorders
Polyneuropathy
|
2.8%
2/72
|
0.00%
0/71
|
|
Nervous system disorders
Radicular syndrome
|
1.4%
1/72
|
0.00%
0/71
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/72
|
1.4%
1/71
|
|
Nervous system disorders
Stupor
|
0.00%
0/72
|
1.4%
1/71
|
|
Nervous system disorders
Syncope
|
1.4%
1/72
|
0.00%
0/71
|
|
Psychiatric disorders
Alcohol withdrawal syndrome
|
0.00%
0/72
|
1.4%
1/71
|
|
Psychiatric disorders
Depression
|
0.00%
0/72
|
1.4%
1/71
|
|
Renal and urinary disorders
Renal failure
|
1.4%
1/72
|
0.00%
0/71
|
|
Renal and urinary disorders
Urinary retention
|
1.4%
1/72
|
0.00%
0/71
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.4%
1/72
|
0.00%
0/71
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/72
|
1.4%
1/71
|
|
Reproductive system and breast disorders
Uterine malposition
|
1.4%
1/72
|
0.00%
0/71
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
1.4%
1/72
|
0.00%
0/71
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.4%
1/72
|
0.00%
0/71
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/72
|
1.4%
1/71
|
|
Vascular disorders
Deep vein thrombosis
|
1.4%
1/72
|
0.00%
0/71
|
Other adverse events
| Measure |
Zoledronic Acid
n=72 participants at risk
Participants received intravenous infusion of Zoledronic acid every 4 weeks for 48 weeks, and calcium and Vitamin D daily.
|
Control
n=71 participants at risk
No treatment with study medication.
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
5.6%
4/72
|
5.6%
4/71
|
|
Gastrointestinal disorders
Constipation
|
6.9%
5/72
|
0.00%
0/71
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
6/72
|
4.2%
3/71
|
|
Gastrointestinal disorders
Nausea
|
8.3%
6/72
|
2.8%
2/71
|
|
General disorders
Chills
|
6.9%
5/72
|
0.00%
0/71
|
|
General disorders
Fatigue
|
9.7%
7/72
|
4.2%
3/71
|
|
General disorders
Influenza like illness
|
9.7%
7/72
|
0.00%
0/71
|
|
General disorders
Oedema peripheral
|
5.6%
4/72
|
4.2%
3/71
|
|
General disorders
Pain
|
6.9%
5/72
|
5.6%
4/71
|
|
General disorders
Pyrexia
|
15.3%
11/72
|
0.00%
0/71
|
|
Infections and infestations
Bronchitis
|
9.7%
7/72
|
5.6%
4/71
|
|
Infections and infestations
Infection
|
5.6%
4/72
|
1.4%
1/71
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
24/72
|
14.1%
10/71
|
|
Infections and infestations
Respiratory tract infection
|
5.6%
4/72
|
4.2%
3/71
|
|
Infections and infestations
Sinusitis
|
4.2%
3/72
|
7.0%
5/71
|
|
Infections and infestations
Urinary tract infection
|
5.6%
4/72
|
1.4%
1/71
|
|
Investigations
Blood creatinine increased
|
6.9%
5/72
|
2.8%
2/71
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
23.6%
17/72
|
12.7%
9/71
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.8%
15/72
|
18.3%
13/71
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
29.2%
21/72
|
5.6%
4/71
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.9%
5/72
|
5.6%
4/71
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
8.3%
6/72
|
5.6%
4/71
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
9/72
|
9.9%
7/71
|
|
Nervous system disorders
Headache
|
15.3%
11/72
|
7.0%
5/71
|
|
Psychiatric disorders
Depression
|
2.8%
2/72
|
5.6%
4/71
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
4/72
|
2.8%
2/71
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
9.7%
7/72
|
1.4%
1/71
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.6%
4/72
|
2.8%
2/71
|
|
Vascular disorders
Hypertension
|
8.3%
6/72
|
2.8%
2/71
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER