Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation

January 29, 2024 updated by: Masonic Cancer Center, University of Minnesota
This is a Phase 2, open-label, randomized, controlled clinical study of pediatric subjects treated with pamidronate with calcium and vitamin D versus calcium and vitamin D alone following hematopoietic cell transplantation (HCT). The purpose of this study is to test the hypothesis that subjects receiving pamidronate with calcium and vitamin D will have higher lumbar spine bone mineral content (LBMC) measured by dual-energy X-ray tomography (DXA) at 1 year post-HCT than subjects receiving calcium and vitamin D alone (Control Group).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • University of Minnesota Amplatz Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Allogeneic hematopoietic cell transplant for hematologic malignancy (i.e. leukemia, lymphoma including ALL, AML, CML, NHL, HL) in complete remission; myelodysplastic syndrome (active dysplasia and/or blasts are permitted, but must not have active leukemia) or idiopathic severe aplastic anemia (SAA)

  • Non-malignant diseases including idiopathic severe aplastic anemia (SAA) and other bone marrow failure disorders, hemoglobinopathies, adrenoleukodystrophy, immune deficiencies/dysregulation disorders who will be receiving myeloablative or reduced toxicity preparative regimens that meet the following criteria:

    • Regimens include those that are TBI based if the TBI dose is > 500cGy single dose or > 800cGy fractionated, or doses <500 cGy if combined with busulfan or treosulfan. These also include chemotherapy only based regimens that contain myeloablative doses of busulfan (>8mg/kg) or treosulfan without TBI.
    • Patients with severe aplastic anemia are eligible regardless of conditioning regimen
  • Myeloablative preparative regimen (for SAA any conditioning therapy allowed)
  • Male or female ≥1 but ≤ 20 years of age at time of study enrollment
  • Patient or parent(s)/legal guardian(s) is able and willing to provide informed consent. Assent will be obtained per local institutional policy. Subjects who turn 18 during the course of the study will be consented at that time of their next visit by a member of the research staff.

Exclusion Criteria:

  • History of a primary bone malignancy involving the lumbar spine
  • Prior and/or planned concomitant medical therapy during the study period (through Day 360 post-HCT) with other bisphosphonates, Denosumab, or Teriparatide
  • Pregnancy or breastfeeding - menstruating females must have a negative pregnancy test prior to study enrollment and agree to repeat pregnancy testing and contraception use per protocol as pamidronate is Pregnancy Category D - positive evidence of human fetal risk based on adverse reaction data
  • Renal insufficiency, defined as creatinine level greater than the upper limit of normal for age
  • Hereditary metabolic bone disease or skeletal dysplasia (e.g., osteopetrosis or OI) or primary hyperparathyroidism
  • Other indications for HCT, including Fanconi anemia, other form of inherited bone marrow failure diseases, metabolic disorder, hemoglobinopathy, or immune deficiency
  • Clinically significant fractures as defined by ISCD (a long bone fracture of the lower extremities, vertebral compression fracture, or two or more long bone fractures of the upper extremities) (88,89) indicated by a cast or a spine x-ray within the last 2 weeks
  • Known or suspected allergy to pamidronate or related products
  • Planned administration of an investigational study drug or agent that either can interact with pamidronate or have an independent effect on bone mineral density within the 4 weeks prior to randomization (Day 90) or planned use during study participation (Day 90 through Day 360)
  • Impending invasive dental procedure that would be expected to occur during study participation (through Day 360)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control group
Subjects will receive a standard recommended dose of calcium and vitamin D.
Drug: Calcium and vitamin D
All subjects will receive a standard recommended dose of 600 IU/day of vitamin D. Subjects who do not meet the RDA will receive additional calcium supplementation.
Other Names:
  • Cholecalciferol
  • Ergocalciferol
Experimental: Pamidronate Group
Subjects randomized to pamidronate treatment will receive infusions approximately 100, 180, and 270 days after HCT along with calcium and vitamin D.
Drug: Calcium and vitamin D
All subjects will receive a standard recommended dose of 600 IU/day of vitamin D. Subjects who do not meet the RDA will receive additional calcium supplementation.
Other Names:
  • Cholecalciferol
  • Ergocalciferol
Drug: Pamidronate
Subjects randomized to pamidronate treatment will receive infusions, 1 mg/kg (to a max dose of 60mg) over 4 hours, every 3 months at approximately 100 days, 180 days, and 270 days after HCT.
Other Names:
  • Aredia
  • Bonapam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Lumbar Spine Bone Mineral Content
Time Frame: 1 year after HCT
1 year after HCT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race)
Time Frame: 1 year after HCT
1 year after HCT
Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT
Time Frame: 1 year after HCT
Measured in g/cm2.
1 year after HCT
Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α)
Time Frame: 7 days, 14 days, 21 days, 90 days after HCT
Measured in pg/ml.
7 days, 14 days, 21 days, 90 days after HCT
Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG]
Time Frame: 7 days, 14 days, 21 days, and 90 days after HCT
Measured in pg/ml.
7 days, 14 days, 21 days, and 90 days after HCT
Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX]
Time Frame: 7, 14, 21, 90, 180, 360 days after HCT
CTX measured in ng/ml.
7, 14, 21, 90, 180, 360 days after HCT
Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP])
Time Frame: 7, 14, 21, 90, 180, 360 days after HCT
P1NP measured in ng/ml.
7, 14, 21, 90, 180, 360 days after HCT
Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG]
Time Frame: 7 days, 14 days, 21 days, and 90 days after HCT
7 days, 14 days, 21 days, and 90 days after HCT
Marker of Bone Resorption Deoxypyridinoline [DPD])
Time Frame: 7, 14, 21, 90, 180, 360 days after HCT
DPD measured in mmol/L.
7, 14, 21, 90, 180, 360 days after HCT
Marker of Bone Formation Osteocalcin [OCN])
Time Frame: 7, 14, 21, 90, 180, 360 days after HCT
OCN measured in pg/ml.
7, 14, 21, 90, 180, 360 days after HCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Investigators

  • Principal Investigator: Kyriakie Sarafoglou, MD, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2015

Primary Completion (Actual)

October 6, 2022

Study Completion (Actual)

October 6, 2022

Study Registration Dates

First Submitted

February 26, 2014

First Submitted That Met QC Criteria

February 26, 2014

First Posted (Estimated)

February 28, 2014

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013LS023

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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