Back to resultsZoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
Primary Purpose
Leukemia, Lymphoma, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
calcium
cholecalciferol
zoledronic acid
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia
Eligibility Criteria
Inclusion Criteria: Patient age ≥18 years Undergoing allogeneic hematopoietic stem cell transplantation (HCT) from any stem cell source with either a myeloablative or non-myeloablative conditioning regimen Bone mineral density measured by baseline pre-transplant DEXA scan in the osteopenic range (defined as a T-score between -1 and -2.5 standard deviation (SD) at either the lumbar spine or the proximal femur or both) Adequate renal function defined as: Calculated creatinine clearance of ≥ 60 ml/min using the Cockcroft-Gault formula: Serum calcium (corrected) of ≤ 10.5 mg/dl Patients (male or female) of reproductive potential are required to use a medically acceptable contraception while receiving zoledronic acid (if assigned study drug). Normal dental exam within the year prior to study registration Informed signed consent to participate in the study Exclusion Criteria: Pre-existing metabolic bone disease including osteomalacia, hyperparathyroid bone disease, osteogenesis imperfecta, Paget's disease, rickets, or hypoparathyroidism. Multiple myeloma History of nontraumatic vertebral compression fractures History of the following endocrine disorders - hyperparathyroidism, hyperthyroidism. Malabsorption syndrome including Crohn's disease. Chronic liver disease Concomitant regular use of phenytoin. Known hypersensitivity to zoledronic acid (Zometa) or other biphosphonates Biphosphonate therapy within the preceding six months. 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) Not pregnant or breastfeeding since zoledronic acid is classified as Pregnancy Category C: risk in pregnancy cannot be ruled out. A negative pregnancy test is required within 7 days of registration if pre- or perimenopausal (i.e., last menstrual period within one year of registration). Because it is not known whether zoledronic acid is excreted in breast milk, breastfeeding is not permitted while receiving study drug.
Sites / Locations
- Masonic Cancer Center at University of Minnesota
- University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm I (control)
Arm II (treatment)
Arm 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.
Outcomes
Primary Outcome Measures
Mean Change in Bone Mineral Density
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.
Secondary Outcome Measures
Mean Change in Serum Osteocalcin
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.
Mean Change in Serum Bone Specific Alkaline Phosphate
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.
Mean Change in Urinary N-terminal Telopeptide
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.
Mean Change in Luteinizing Hormone
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.
Mean Change in Follicle-Stimulating Hormone
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.
Mean Change in Thyroid Function Test 4
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.
Mean Change in Ultrasensitive Estradiol
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.
Mean Change in Total Testosterone
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00321932
Brief Title
Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
Official Title
A Randomized Phase II of Zoledronic Acid (Zometa) in the Prevention of Osteoporosis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Zoledronic acid, vitamin D, and calcium may prevent bone loss in patients who are undergoing donor stem cell transplant.
PURPOSE: This randomized phase II trial is studying how well zoledronic acid works in preventing osteoporosis in patients undergoing donor stem cell transplant.
Detailed Description
OBJECTIVES:
Primary
Evaluate whether prophylactic administration of zoledronic acid can reduce the severity of bone mineral loss in patients undergoing allogeneic hematopoietic stem cell transplantation.
Secondary
Determine the safety of zoledronic acid in these patients.
OUTLINE: This is a multicenter, open-label, prospective, randomized, controlled study. Patients are stratified according to participating center and type of transplant (myeloablative vs nonmyeloablative). Patients are randomized to 1 of 2 treatment arms.
Arm I (control): Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Arm II (treatment): 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.
In both arms, treatment continues in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 12 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Myelodysplastic Syndromes, Osteoporosis, Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (control)
Arm Type
Active Comparator
Arm Description
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
Arm Title
Arm II (treatment)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
calcium
Other Intervention Name(s)
calcium carbonate, calcium citrate, calcium gluconate
Intervention Description
All randomized patients (control and study drug) will take 1000 mg of calcium and 400 - 500 International Units (IU) of vitamin D orally each day, beginning as soon as possible after study enrollment. These supplements may be taken either in the morning or in the evening with food. Participants will continue taking the supplements on a daily basis until the final study visit (approximately 12 months after the transplant date).
Intervention Type
Dietary Supplement
Intervention Name(s)
cholecalciferol
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
Zometa(R)
Intervention Description
Zoledronic acid (Zometa®) will be administered after randomization (but within 28 days prior to transplant) and at 3 and 6 months after the transplant for a total of 3 doses. The dose of Zometa will be 4 mg intravenous in 100 ml of sterile 0.9% sodium chloride, United States Pharmacopeia (USP), or 5% dextrose, USP infused over a minimum of 15 minutes for patients with a calculated creatinine clearance of ≥60 mL/min. The drug may be administered through a peripheral or a central intravenous line.
Primary Outcome Measure Information:
Title
Mean Change in Bone Mineral Density
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
Secondary Outcome Measure Information:
Title
Mean Change in Serum Osteocalcin
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
Title
Mean Change in Serum Bone Specific Alkaline Phosphate
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
Title
Mean Change in Urinary N-terminal Telopeptide
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
Title
Mean Change in Luteinizing Hormone
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
Title
Mean Change in Follicle-Stimulating Hormone
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
Title
Mean Change in Thyroid Function Test 4
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
Title
Mean Change in Ultrasensitive Estradiol
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
Title
Mean Change in Total Testosterone
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient age ≥18 years
Undergoing allogeneic hematopoietic stem cell transplantation (HCT) from any stem cell source with either a myeloablative or non-myeloablative conditioning regimen
Bone mineral density measured by baseline pre-transplant DEXA scan in the osteopenic range (defined as a T-score between -1 and -2.5 standard deviation (SD) at either the lumbar spine or the proximal femur or both)
Adequate renal function defined as: Calculated creatinine clearance of ≥ 60 ml/min using the Cockcroft-Gault formula:
Serum calcium (corrected) of ≤ 10.5 mg/dl
Patients (male or female) of reproductive potential are required to use a medically acceptable contraception while receiving zoledronic acid (if assigned study drug).
Normal dental exam within the year prior to study registration
Informed signed consent to participate in the study
Exclusion Criteria:
Pre-existing metabolic bone disease including osteomalacia, hyperparathyroid bone disease, osteogenesis imperfecta, Paget's disease, rickets, or hypoparathyroidism.
Multiple myeloma
History of nontraumatic vertebral compression fractures
History of the following endocrine disorders - hyperparathyroidism, hyperthyroidism.
Malabsorption syndrome including Crohn's disease.
Chronic liver disease
Concomitant regular use of phenytoin.
Known hypersensitivity to zoledronic acid (Zometa) or other biphosphonates
Biphosphonate therapy within the preceding six months.
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)
Not pregnant or breastfeeding since zoledronic acid is classified as Pregnancy Category C: risk in pregnancy cannot be ruled out. A negative pregnancy test is required within 7 days of registration if pre- or perimenopausal (i.e., last menstrual period within one year of registration). Because it is not known whether zoledronic acid is excreted in breast milk, breastfeeding is not permitted while receiving study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linda J. Burns, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Study Chair
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792-6164
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
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