Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT02074631
Collaborator
(none)
80
2
2
83
40
0.5

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation
Actual Study Start Date :
Feb 1, 2015
Actual Primary Completion Date :
Dec 31, 2021
Actual Study Completion Date :
Dec 31, 2021

Arms and Interventions

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: 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
  • 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
  • Outcome Measures

    Primary Outcome Measures

    1. Lumbar spine bone mineral content [1 year after HCT]

    Secondary Outcome Measures

    1. Total body bone mineral content (TBMC; excluding head; adjusted for height, age, sex, Tanner stage, and race) [1 year after HCT]

    2. Total bone mineral density (BMD), cortical BMD, trabecular BMD, and estimated bone strength measured by pQCT [1 year after HCT]

    3. Cytokine levels (interleukin IL-6, IL-7, and TNF-α) [7 days, 14 days, 21 days, 100 days after HCT]

    4. Receptor activator of the nuclear factor-κB ligand [RANKL], osteoprotegerin [OPG], RANKL/OPG ratio [7 days, 14 days, 21 days, and 100 days after HCT]

    5. Markers of bone resorption (carboxy-terminal collagen crosslinks [CTX] and deoxypyridinoline [DPD]) [7, 14, 21, 100, 180, 360 days after HCT]

    6. Markers of bone formation (procollagen type 1 N-terminal propeptide [P1NP] and osteocalcin [OCN]) [7, 14, 21, 100, 180, 360 days after HCT]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 20 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Minnesota Amplatz Children's Hospital Minneapolis Minnesota United States 55454
    2 Seattle Children's Hospital Seattle Washington United States 98105

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT02074631
    Other Study ID Numbers:
    • 2013LS023
    First Posted:
    Feb 28, 2014
    Last Update Posted:
    Apr 18, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Masonic Cancer Center, University of Minnesota
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 18, 2022