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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

Tracking Information
First Submitted Date  ICMJE May 2, 2006
First Posted Date  ICMJE May 4, 2006
Results First Submitted Date  ICMJE May 4, 2012
Results First Posted Date  ICMJE October 26, 2012
Last Update Posted Date March 9, 2017
Study Start Date  ICMJE July 2005
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2012)
Mean Change in Bone Mineral Density [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00321932 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2012)
  • Mean Change in Serum Osteocalcin [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
Official Title  ICMJE A Randomized Phase II of Zoledronic Acid (Zometa) in the Prevention of Osteoporosis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Osteoporosis
  • Ovarian Cancer
Intervention  ICMJE
  • Dietary Supplement: calcium
    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).
    Other Names:
    • calcium carbonate
    • calcium citrate
    • calcium gluconate
  • Dietary Supplement: cholecalciferol
    Given orally
  • Drug: zoledronic acid
    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.
    Other Name: Zometa(R)
Study Arms  ICMJE
  • Active Comparator: Arm I (control)
    Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
    Interventions:
    • Dietary Supplement: calcium
    • Dietary Supplement: cholecalciferol
  • Experimental: 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.
    Interventions:
    • Dietary Supplement: calcium
    • Dietary Supplement: cholecalciferol
    • Drug: zoledronic acid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 26, 2012)
61
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00321932
Other Study ID Numbers  ICMJE 2005NT018
UMN-0506M70866 ( Other Identifier: IRB, University of Minnesota )
UMN-MT2005-06 ( Other Identifier: Blood and Marrow Transplantation Program )
NOVARTIS-CZOL446EUS29 ( Other Identifier: Novartis )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Minnesota - Clinical and Translational Science Institute
Study Sponsor  ICMJE University of Minnesota - Clinical and Translational Science Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Linda J. Burns, MD Masonic Cancer Center, University of Minnesota
PRS Account University of Minnesota - Clinical and Translational Science Institute
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP