Clinical trial NCT00321932: Zoledronic Acid in Preventing Osteoporosis in Patients Undergoing Donor Stem Cell Transplant
Official title: A Randomized Phase II of Zoledronic Acid (Zometa) in the Prevention of Osteoporosis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Myelodysplastic Syndromes
Osteoporosis
Ovarian Cancer
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2006-05-04
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Change in Bone Mineral Density
timeFrame: From Time of Transplant to 12 Months Post-Transplant
Secondary outcomes:
measure: Mean Change in Serum Osteocalcin
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Serum Bone Specific Alkaline Phosphate
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Urinary N-terminal Telopeptide
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Luteinizing Hormone
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Follicle-Stimulating Hormone
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Thyroid Function Test 4
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Ultrasensitive Estradiol
timeFrame: From Time of Transplant to 12 Months Post-Transplant
measure: Mean Change in Total Testosterone
timeFrame: From Time of Transplant to 12 Months Post-Transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Linda J. Burns, MD
role: STUDY_CHAIR
References: