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Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT00321932
Recruitment Status : Completed
First Posted : May 4, 2006
Results First Posted : October 26, 2012
Last Update Posted : March 9, 2017
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukemia
Lymphoma
Myelodysplastic Syndromes
Osteoporosis
Ovarian Cancer
Interventions Dietary Supplement: calcium
Dietary Supplement: cholecalciferol
Drug: zoledronic acid
Enrollment 61
Recruitment Details Patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) at participating institutions were offered this trial. If the patient met study requirements, the patient was registered and randomized.
Pre-assignment Details  
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months. Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid IV over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Period Title: Overall Study
Started 29 32
Completed 19 11
Not Completed 10 21
Reason Not Completed
Death             3             6
Withdrawal by Subject             3             6
Early relapse             2             8
Missing data             2             1
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa) Total
Hide Arm/Group Description Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months. Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid IV over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation. Total of all reporting groups
Overall Number of Baseline Participants 29 32 61
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 32 participants 61 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
29
 100.0%
32
 100.0%
61
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 32 participants 61 participants
51  (10) 51  (12) 51  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 32 participants 61 participants
Female
13
  44.8%
9
  28.1%
22
  36.1%
Male
16
  55.2%
23
  71.9%
39
  63.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 29 participants 32 participants 61 participants
29 32 61
1.Primary Outcome
Title Mean Change in Bone Mineral Density
Hide Description

Change in bone mineral density of the femoral neck measured from baseline to 12 months after transplant utilizing Dual-energy X-ray absorptiometry (DEXA) scan. Comparison of difference between the standard of care group (receiving calcium and vitamin D)and the Zometa group. The measurement consists of baseline bone mineral density measurements with followup measurements at 12 months.

This will be analyzed as a continuous variable. Percent change in bone mineral density (BMD) will be calculated as (BMD change) x 100/BMD baseline.

Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: percent
-0.0714  (0.101) -0.0036  (0.089)
2.Secondary Outcome
Title Mean Change in Serum Osteocalcin
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. As osteocalcin is produced by osteoblasts, it is often used as a marker for the bone formation process.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV)( over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: ng/ml
-3.6  (24.1) -11.3  (7.6)
3.Secondary Outcome
Title Mean Change in Serum Bone Specific Alkaline Phosphate
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. The decrease in serum bone-specific alkaline phosphatase predicts bone mineral density response to hormone replacement therapy in early postmenopausal women.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: U/L
-3.0  (5.7) -4.3  (5.6)
4.Secondary Outcome
Title Mean Change in Urinary N-terminal Telopeptide
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. In bone physiology, the N-terminal telopeptide is a biomarker used to measure the rate of bone turnover.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: nM Bone Collagen Equivalents/mM creatini
-22.5  (137.7) -103.0  (137.7)
5.Secondary Outcome
Title Mean Change in Luteinizing Hormone
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Luteinizing hormone is a hormone produced by the anterior pituitary gland.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: IU/L
18.8  (21.6) 12.8  (16.8)
6.Secondary Outcome
Title Mean Change in Follicle-Stimulating Hormone
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Follicle-stimulating hormone is a hormone produced by the anterior pituitary gland.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: IU/L
14.0  (46.7) 6.6  (6.5)
7.Secondary Outcome
Title Mean Change in Thyroid Function Test 4
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Individuals who have hyperthyroidism will have an elevated thyroxine (FT4). Low serum thyroxine can also indicate a pituitary problem.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: ng/dL
-0.6  (2.2) -0.2  (0.9)
8.Secondary Outcome
Title Mean Change in Ultrasensitive Estradiol
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. In women estradiol is responsible for growth of the breast and reproductive epithelia, maturation of long bones and development of the secondary sexual characteristics.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: pg/ml
-3.6  (19.4) -6.3  (21.0)
9.Secondary Outcome
Title Mean Change in Total Testosterone
Hide Description Change in bone resorption markers of bone metabolism measured at baseline and 12 months post transplant for all enrolled patients. Testosterone affects the brain, bone and muscle mass, fat distribution, the vascular system, energy levels, genital tissues, and sexual functioning.
Time Frame From Time of Transplant to 12 Months Post-Transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description:
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid intravenously (IV) over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
Overall Number of Participants Analyzed 29 32
Mean (Standard Deviation)
Unit of Measure: ng/dL
-65.4  (130.4) -23.6  (140.0)
Time Frame Serious adverse events are collected from first dose of study medication through 30 days of the last dose of treatment. Any death that occured within one year of first treatment is also included.
Adverse Event Reporting Description Adverse reactions to Zometa® (zoledronic acid for injection) are usually mild and transient and similar to those reported for other bisphosphonates. Therefore, only serious events were collected.
 
Arm/Group Title Arm I (Standard of Care) Arm II (Treatment With Zometa)
Hide Arm/Group Description Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months. Patients receive vitamin D and calcium as in arm I. Patients also receive zoledronic acid IV over 15-30 minutes at 28 days prior to stem cell transplantation and at 3 and 6 months after transplantation.
All-Cause Mortality
Arm I (Standard of Care) Arm II (Treatment With Zometa)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Standard of Care) Arm II (Treatment With Zometa)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/29 (27.59%)      21/32 (65.63%)    
Blood and lymphatic system disorders     
Graft-versus-host disease  1  0/29 (0.00%)  0 2/32 (6.25%)  2
Nosebleed  1  1/29 (3.45%)  1 0/32 (0.00%)  0
Pseudomonas sepsis  1  0/29 (0.00%)  0 1/32 (3.13%)  1
General disorders     
Death  1  6/29 (20.69%)  6 15/32 (46.88%)  15
Infections and infestations     
Infection with unknown absolute neutrophil count  1 [1]  0/29 (0.00%)  0 2/32 (6.25%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
New Malignancy  1  0/29 (0.00%)  0 1/32 (3.13%)  1
Respiratory, thoracic and mediastinal disorders     
Idiopathic pulmonary syndrome  1  1/29 (3.45%)  1 0/32 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Pneumonia
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I (Standard of Care) Arm II (Treatment With Zometa)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/0      0/0    
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Linda Burns, M.D.
Organization: Masonic Cancer Center, University of Minnesota
Phone: 612-624-8144
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00321932     History of Changes
Other Study ID Numbers: 2005NT018
UMN-0506M70866 ( Other Identifier: IRB, University of Minnesota )
UMN-MT2005-06 ( Other Identifier: Blood and Marrow Transplantation Program )
NOVARTIS-CZOL446EUS29 ( Other Identifier: Novartis )
First Submitted: May 2, 2006
First Posted: May 4, 2006
Results First Submitted: May 4, 2012
Results First Posted: October 26, 2012
Last Update Posted: March 9, 2017