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

University of Minnesota (UMN)

Status and phase: Completed; Phase 2

Conditions: Osteoporosis; Lymphoma; Ovarian Cancer; Leukemia; Myelodysplastic Syndromes

Treatments: Dietary Supplement: cholecalciferol; Drug: zoledronic acid; Dietary Supplement: calcium

Study type: Interventional

Funder types: Other

Identifiers

NCT00321932

UMN-0506M70866 (Other Identifier)

NOVARTIS-CZOL446EUS29 (Other Identifier)

2005NT018

UMN-MT2005-06 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 61 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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61 participants in 2 patient groups

Arm I (control)

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: calcium

Dietary Supplement: cholecalciferol

Arm II (treatment)

Experimental group

Description:

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.

Treatment:

Dietary Supplement: calcium

Dietary Supplement: cholecalciferol

Drug: zoledronic acid