Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
Condition: Leukemia; Lymphoma; Myelodysplastic Syndromes; Osteoporosis; Ovarian Cancer
MeSH terms: Osteoporosis; Myelodysplastic Syndromes
Intervention: calcium; cholecalciferol; zoledronic acid
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).; Given orally; 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.
Intervention MeSH terms: Calcium, Dietary; Cholecalciferol; Zoledronic Acid; Calcium Carbonate; Calcium
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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.