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OsteopeniaPhase 2NCT02074631

Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation

A Phase 2 study testing Pamidronate and Calcium and vitamin D in people with Osteopenia and Osteoporosis, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 1 year to 20 years
Conditions the study is for
Osteopenia, Osteoporosis
What is being tested?
Pamidronate and Calcium and vitamin D
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
2 sitesUnited States
Study dates
Feb 2015to 6 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 20 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 10Show fewer
  • 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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • University of Minnesota Amplatz Children's Hospital

    Minneapolis, Minnesota, 55454

  • Seattle Children's Hospital

    Seattle, Washington, 98105

Other trials in United States

About this study

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).

Being tested
Pamidronate, Calcium and vitamin D
Keywords
bone mineral content, bone mineral density, bone formation, bone resorption, pamidronate, children, DXA, bone marrow transplant
Medical subject headings
Bone Diseases, Metabolic, Osteoporosis, Bone Resorption

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PamidronateDrug

    Also called Aredia, Bonapam

    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.

  • Calcium and vitamin DDrug

    Also called Cholecalciferol, Ergocalciferol

    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.

Study groups in NCT02074631
Study groupRoleWhat they receive
Control groupActive comparatorSubjects will receive a standard recommended dose of calcium and vitamin D.
Receives: Drug: Calcium and vitamin D
Pamidronate GroupExperimentalSubjects randomized to pamidronate treatment will receive infusions approximately 100, 180, and 270 days after HCT along with calcium and vitamin D.
Receives: Drug: Pamidronate; Drug: Calcium and vitamin D

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Lumbar Spine Bone Mineral Content

    Measured: 1 year after HCT

Secondary outcomes (9)
  1. Total Body Bone Mineral Content (TBMC; Excluding Head; Adjusted for Height, Age, Sex, Tanner Stage, and Race)

    Measured: 1 year after HCT

  2. Total Bone Mineral Density (BMD), Cortical BMD, Trabecular BMD, and Estimated Bone Strength Measured by pQCT

    Measured in g/cm2.

    Measured: 1 year after HCT

  3. Cytokine Levels (Interleukin IL-6, IL-7, and TNF-α)

    Measured in pg/ml.

    Measured: 7 days, 14 days, 21 days, 90 days after HCT

  4. Receptor Activator of the Nuclear Factor-κB Ligand [RANKL], Osteoprotegerin [OPG]

    Measured in pg/ml.

    Measured: 7 days, 14 days, 21 days, and 90 days after HCT

  5. Marker of Bone Resorption (Carboxy-terminal Collagen Crosslinks [CTX]

    CTX measured in ng/ml.

    Measured: 7, 14, 21, 90, 180, 360 days after HCT

  6. Markers of Bone Formation (Procollagen Type 1 N-terminal Propeptide [P1NP])

    P1NP measured in ng/ml.

    Measured: 7, 14, 21, 90, 180, 360 days after HCT

  7. Ratio of Receptor Activator of the Nuclear Factor-κB Ligand [RANKL] and Osteoprotegerin [OPG]

    Measured: 7 days, 14 days, 21 days, and 90 days after HCT

  8. Marker of Bone Resorption Deoxypyridinoline [DPD])

    DPD measured in mmol/L.

    Measured: 7, 14, 21, 90, 180, 360 days after HCT

  9. Marker of Bone Formation Osteocalcin [OCN])

    OCN measured in pg/ml.

    Measured: 7, 14, 21, 90, 180, 360 days after HCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2014 (estimated)
  2. Study startFeb 2015
  3. Primary completion6 Oct 2022
  4. Study completion6 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02074631
Sponsor's protocol ID
2013LS023
Status last verified
Jan 2024
First submitted
26 Feb 2014
Last updated
20 Feb 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Petryk A, Bergemann TL, Polga KM, Ulrich KJ, Raatz SK, Brown DM, Robison LL, Baker KS. Prospective study of changes in bone mineral density and turnover in children after hematopoietic cell transplantation. J Clin Endocrinol Metab. 2006 Mar;91(3):899-905. doi: 10.1210/jc.2005-1927. Epub 2005 Dec 13.

    PubMed 16352681
  • Bhatia S, Ramsay NK, Weisdorf D, Griffiths H, Robison LL. Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies. Bone Marrow Transplant. 1998 Jul;22(1):87-90. doi: 10.1038/sj.bmt.1701275.

    PubMed 9678801
  • Nysom K, Holm K, Michaelsen KF, Hertz H, Jacobsen N, Muller J, Molgaard C. Bone mass after allogeneic BMT for childhood leukaemia or lymphoma. Bone Marrow Transplant. 2000 Jan;25(2):191-6. doi: 10.1038/sj.bmt.1702131.

    PubMed 10673679
  • Kaste SC, Shidler TJ, Tong X, Srivastava DK, Rochester R, Hudson MM, Shearer PD, Hale GA. Bone mineral density and osteonecrosis in survivors of childhood allogeneic bone marrow transplantation. Bone Marrow Transplant. 2004 Feb;33(4):435-41. doi: 10.1038/sj.bmt.1704360.

    PubMed 14716354
  • Perkins JL, Kunin-Batson AS, Youngren NM, Ness KK, Ulrich KJ, Hansen MJ, Petryk A, Steinberger J, Anderson FS, Baker KS. Long-term follow-up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr Blood Cancer. 2007 Dec;49(7):958-63. doi: 10.1002/pbc.21207.

    PubMed 17474113
  • Daniels MW, Wilson DM, Paguntalan HG, Hoffman AR, Bachrach LK. Bone mineral density in pediatric transplant recipients. Transplantation. 2003 Aug 27;76(4):673-8. doi: 10.1097/01.TP.0000076627.70050.53.

    PubMed 12973107
  • Mostoufi-Moab S, Ginsberg JP, Bunin N, Zemel B, Shults J, Leonard MB. Bone density and structure in long-term survivors of pediatric allogeneic hematopoietic stem cell transplantation. J Bone Miner Res. 2012 Apr;27(4):760-9. doi: 10.1002/jbmr.1499.

    PubMed 22189761
  • Jackowski SA, Kontulainen SA, Cooper DM, Lanovaz JL, Baxter-Jones AD. The timing of BMD and geometric adaptation at the proximal femur from childhood to early adulthood in males and females: a longitudinal study. J Bone Miner Res. 2011 Nov;26(11):2753-61. doi: 10.1002/jbmr.468.

    PubMed 21773991
  • Kaste SC, Rai SN, Fleming K, McCammon EA, Tylavsky FA, Danish RK, Rose SR, Sitter CD, Pui CH, Hudson MM. Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2006 Jan;46(1):77-87. doi: 10.1002/pbc.20553.

    PubMed 16106430
  • Ross PD, Davis JW, Epstein RS, Wasnich RD. Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med. 1991 Jun 1;114(11):919-23. doi: 10.7326/0003-4819-114-11-919.

    PubMed 2024857
  • Baxter-Jones AD, Faulkner RA, Forwood MR, Mirwald RL, Bailey DA. Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass. J Bone Miner Res. 2011 Aug;26(8):1729-39. doi: 10.1002/jbmr.412.

    PubMed 21520276
  • Polgreen LE, Rudser K, Deyo M, Smith A, Baker KS, Petryk A. Changes in biomarkers of bone resorption over the first six months after pediatric hematopoietic cell transplantation. Pediatr Transplant. 2012 Dec;16(8):852-7. doi: 10.1111/j.1399-3046.2012.01780.x. Epub 2012 Aug 20.

    PubMed 22905997
  • Grigg AP, Shuttleworth P, Reynolds J, Schwarer AP, Szer J, Bradstock K, Hui C, Herrmann R, Ebeling PR. Pamidronate reduces bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab. 2006 Oct;91(10):3835-43. doi: 10.1210/jc.2006-0684. Epub 2006 Jul 11.

    PubMed 16835281
  • Kananen K, Volin L, Laitinen K, Alfthan H, Ruutu T, Valimaki MJ. Prevention of bone loss after allogeneic stem cell transplantation by calcium, vitamin D, and sex hormone replacement with or without pamidronate. J Clin Endocrinol Metab. 2005 Jul;90(7):3877-85. doi: 10.1210/jc.2004-2161. Epub 2005 Mar 29.

    PubMed 15797959
  • Glorieux FH. Treatment of osteogenesis imperfecta: who, why, what? Horm Res. 2007;68 Suppl 5:8-11. doi: 10.1159/000110463. Epub 2007 Dec 10.

    PubMed 18174695

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pamidronate and Calcium and vitamin D in people with Osteopenia and Osteoporosis, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lumbar Spine Bone Mineral Content (time frame: 1 year after HCT). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02074631, which also lists 55 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.

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