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

NCT ID: NCT00321932

Last Updated: 2017-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2012-03-31

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.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Osteoporosis; Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (control)

Patients receive oral cholecalciferol (vitamin D) and oral calcium once a day for 12 months.

Group Type: ACTIVE_COMPARATOR

calcium

Intervention Type: DIETARY_SUPPLEMENT

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).

cholecalciferol

Intervention Type: DIETARY_SUPPLEMENT

Given orally

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.

Group Type: EXPERIMENTAL

calcium

Intervention Type: DIETARY_SUPPLEMENT

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).

cholecalciferol

Intervention Type: DIETARY_SUPPLEMENT

Given orally

zoledronic acid

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: DIETARY_SUPPLEMENT

cholecalciferol

Given orally

Intervention Type: DIETARY_SUPPLEMENT

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.

Intervention Type: DRUG

Other Intervention Names

calcium carbonate; calcium citrate; calcium gluconate; Zometa(R)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Linda J. Burns, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

UMN-0506M70866

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-MT2005-06

Identifier Type: OTHER

Identifier Source: secondary_id

NOVARTIS-CZOL446EUS29

Identifier Type: OTHER

Identifier Source: secondary_id

2005NT018

Identifier Type: -

Identifier Source: org_study_id