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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00321932
First received: May 2, 2006
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Osteoporosis
Ovarian Cancer
Dietary Supplement: calcium
Dietary Supplement: cholecalciferol
Drug: zoledronic acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II of Zoledronic Acid (Zometa) in the Prevention of Osteoporosis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Mean Change in Bone Mineral Density [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ] [ Designated as safety issue: No ]

    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 [ Time Frame: From Time of Transplant to 12 Months Post-Transplant ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 61
Study Start Date: July 2005
Study Completion Date: March 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (control)
Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.
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
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.
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00321932

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: Linda J. Burns, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00321932     History of Changes
Other Study ID Numbers: 2005NT018, UMN-0506M70866, UMN-MT2005-06, NOVARTIS-CZOL446EUS29
Study First Received: May 2, 2006
Results First Received: May 4, 2012
Last Updated: September 26, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Osteoporosis
Ovarian Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Zoledronic acid
Calcium, Dietary
Cholecalciferol

ClinicalTrials.gov processed this record on April 16, 2014