Prevention of Bone Loss After Pediatric Hematopoietic Cell Transplantation

Phase 2

Completed

Conditions: Osteopenia
Osteoporosis

Interventions: Drug: Pamidronate
Drug: Calcium and vitamin D

Registration Number: NCT02074631

Lead Sponsor: Masonic Cancer Center, University of Minnesota

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pamidronate Group	Calcium and vitamin D	Subjects randomized to pamidronate treatment will receive infusions approximately 100, 180, and 270 days after HCT along with calcium and vitamin D.
Control group	Calcium and vitamin D	Subjects will receive a standard recommended dose of calcium and vitamin D.
Pamidronate Group	Pamidronate	Subjects randomized to pamidronate treatment will receive infusions approximately 100, 180, and 270 days after HCT along with calcium and vitamin D.

Primary Outcome Measures

Name	Time	Method
Lumbar Spine Bone Mineral Content	1 year after HCT

Secondary Outcome Measures

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

Trial Locations

Locations (2): University of Minnesota Amplatz Children's Hospital
🇺🇸
Minneapolis, Minnesota, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States