Trial Outcomes & Findings for Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant (NCT NCT00321932)
NCT ID: NCT00321932
Last Updated: 2017-03-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
61 participants
Primary outcome timeframe
From Time of Transplant to 12 Months Post-Transplant
Results posted on
2017-03-09
Participant Flow
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.
Participant milestones
| Measure |
Arm I (Standard of Care)
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
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.
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
32
|
|
Overall Study
COMPLETED
|
19
|
11
|
|
Overall Study
NOT COMPLETED
|
10
|
21
|
Reasons for withdrawal
| Measure |
Arm I (Standard of Care)
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
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.
|
|---|---|---|
|
Overall Study
Death
|
3
|
6
|
|
Overall Study
Withdrawal by Subject
|
3
|
6
|
|
Overall Study
Early relapse
|
2
|
8
|
|
Overall Study
Missing data
|
2
|
1
|
Baseline Characteristics
Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
Baseline characteristics by cohort
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 10 • n=5 Participants
|
51 years
STANDARD_DEVIATION 12 • n=7 Participants
|
51 years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=5 Participants
|
32 participants
n=7 Participants
|
61 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Bone Mineral Density
|
-0.0714 percent
Standard Deviation 0.101
|
-0.0036 percent
Standard Deviation 0.089
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Serum Osteocalcin
|
-3.6 ng/ml
Standard Deviation 24.1
|
-11.3 ng/ml
Standard Deviation 7.6
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Serum Bone Specific Alkaline Phosphate
|
-3.0 U/L
Standard Deviation 5.7
|
-4.3 U/L
Standard Deviation 5.6
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Urinary N-terminal Telopeptide
|
-22.5 nM Bone Collagen Equivalents/mM creatini
Standard Deviation 137.7
|
-103.0 nM Bone Collagen Equivalents/mM creatini
Standard Deviation 137.7
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Luteinizing Hormone
|
18.8 IU/L
Standard Deviation 21.6
|
12.8 IU/L
Standard Deviation 16.8
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Follicle-Stimulating Hormone
|
14.0 IU/L
Standard Deviation 46.7
|
6.6 IU/L
Standard Deviation 6.5
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Thyroid Function Test 4
|
-0.6 ng/dL
Standard Deviation 2.2
|
-0.2 ng/dL
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Ultrasensitive Estradiol
|
-3.6 pg/ml
Standard Deviation 19.4
|
-6.3 pg/ml
Standard Deviation 21.0
|
SECONDARY outcome
Timeframe: From Time of Transplant to 12 Months Post-TransplantChange 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.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=29 Participants
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 Participants
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.
|
|---|---|---|
|
Mean Change in Total Testosterone
|
-65.4 ng/dL
Standard Deviation 130.4
|
-23.6 ng/dL
Standard Deviation 140.0
|
Adverse Events
Arm I (Standard of Care)
Serious events: 8 serious events
Other events: 0 other events
Deaths: 0 deaths
Arm II (Treatment With Zometa)
Serious events: 21 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm I (Standard of Care)
n=29 participants at risk
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
|
Arm II (Treatment With Zometa)
n=32 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Nosebleed
|
3.4%
1/29 • Number of events 1 • 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 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.
|
0.00%
0/32 • 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 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.
|
|
Blood and lymphatic system disorders
Pseudomonas sepsis
|
0.00%
0/29 • 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 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.
|
3.1%
1/32 • Number of events 1 • 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 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.
|
|
General disorders
Death
|
20.7%
6/29 • Number of events 6 • 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 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.
|
46.9%
15/32 • Number of events 15 • 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 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.
|
|
Blood and lymphatic system disorders
Graft-versus-host disease
|
0.00%
0/29 • 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 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.
|
6.2%
2/32 • Number of events 2 • 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 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.
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary syndrome
|
3.4%
1/29 • Number of events 1 • 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 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.
|
0.00%
0/32 • 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 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.
|
|
Infections and infestations
Infection with unknown absolute neutrophil count
|
0.00%
0/29 • 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 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.
|
6.2%
2/32 • Number of events 2 • 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 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
New Malignancy
|
0.00%
0/29 • 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 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.
|
3.1%
1/32 • Number of events 1 • 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 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.
|
Other adverse events
Adverse event data not reported
Additional Information
Linda Burns, M.D.
Masonic Cancer Center, University of Minnesota
Phone: 612-624-8144
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place