Zoledronate to Prevent Bone Health Complications in Pediatric Hematopoietic Stem Cell Transplant Survivors

Official title

Early Intervention With Zoledronate to Safely Prevent Bone Health Complications in Pediatric Hematopoietic Stem Cell Transplant Survivors

Overview

The purpose of this pilot study is to investigate the safety and preliminarily assess efficacy of early intervention with zoledronate in high risk pediatric hematopoietic stem cell transplantation (HSCT) patients to prevent the development of bone disease and fractures and reduce potential pain and suffering.

Detailed description

Bone disease, including low bone density and fragility fractures (osteoporosis), is common among survivors of pediatric hematopoietic stem cell transplantation (HSCT). Further, patients who develop graft-versus-host disease (GVHD) following HSCT or who have high cumulative doses of glucocorticoids are at even higher risk to develop bone complications. Recent data also suggest that a large number of HSCT candidates arrive to transplantation already with low bone mineral density, adding to the potential risk of developing bone disease following HSCT. Typically, treatment for osteoporosis in children using bisphosphonates, such as zoledronate, is recommended only after the development of fragility fractures.

The investigators propose to study the safety and efficacy of a novel method of early intervention with zoledronate in high risk pediatric HSCT patients to prevent the development of bone disease and fractures in order to reduce potential pain and suffering.

Interventions

• Drug Zoledronate
  Zoledronate is in the class of drugs entitled bisphosphonates which act to inhibit bone resorption by inhibiting osteoclast activity therefore reducing bone turnover.

Primary outcome measures

• Safety of early intervention Zoledronate [Time frame: At the time of infusion through up to 60 days post last dose of Zoledronate]
• Feasibility of early intervention Zoledronate [Time frame: At patient discharge, typically 1 week post infusion]

Secondary outcome measures (2)

• Bone health efficiency [Time frame: Baseline, +6 months, and +12 months]
• Bone substrate turnover [Time frame: Baseline and +30 days]

Eligibility criteria

Inclusion criteria

• Patients ≥5 and ≤18 years old who are preparing for HSCT with a height-for-age corrected DXA Z-score of <-2.0 and admitted to a CCHMC inpatient unit.
• Patients ≥5 and ≤18 years old recovering from HSCT and who have developed de novo acute or chronic GVHD and are admitted to a CCHMC inpatient unit.

Exclusion criteria

• Age <5 years and >18 years
• Patients with Fanconi anemia or other radiation-sensitive syndromes with increased malignancy risk
• history of prior bisphosphonate use
• low 25-OH vitamin D levels (<20 ng/mL)
• active febrile illness
• uncontrolled infection
• Elevated creatinine at the time of enrollment, history or renal failure, or documented low glomerular filtration rate (GFR≤90)
• Active bone disease including history of abnormal PTH level for any reason, active bone fracture/healing, or primary disorder of bone development or metabolism.
• Women who are pregnant or breast feeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Cincinnati Children's Hospital Medical Center — Cincinnati

Identifiers

NCT: NCT07375290 · 2023-0052

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗