A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT
Condition: Vitamin D Deficiency; Stem Cell Transplant Complications; Pediatric Cancer; Blood Disorder; Pediatric Acute Myeloid Leukemia; Pediatric Acute Lymphoid Leukemia; Myelodysplastic Syndromes; Sickle Cell Anemia in Children; Aplastic Anemia; Thalassemia in Children
MeSH terms: Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia; Myelodysplastic Syndromes; Thalassemia; Anemia, Aplastic; Anemia, Sickle Cell; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      Research has suggested that children with sufficient vitamin D levels undergoing
      hematopoietic stem cell transplant (HSCT) have improved outcomes, including lower incidences
      of infection and graft-versus-host disease (GVHD), as well as overall improved survival.
      However, supplementation in children undergoing HSCT has shown to be a challenge using
      standard or aggressive supplementation strategies. The primary objective of this study is to
      determine the safety and efficacy of a single, high dose oral vitamin D (Stoss Therapy) at
      the start of transplant followed by maintenance supplementation in children undergoing HSCT.
    

Detailed description: 
      Comorbidities and complications including infection, organ system toxicity, graft-versus-host
      disease (GVHD) and disease recurrence are some of the biggest contributors to quality of life
      and mortality in children undergoing hematopoietic stem cell transplant (HSCT). Research has
      suggested that patients with sufficient vitamin D levels during transplant have improved
      outcomes, including lower incidences of infection and acute GVHD, as well as overall improved
      survival. Prior research has shown that chronically ill children are at risk for vitamin D
      deficiency, including those undergoing HSCT. Data has shown populations with as many as 70%
      of HSCT patients have insufficient levels of vitamin D at time of transplant. While several
      studies have attempted methods of vitamin D supplementation in this subset of patients, there
      has not been success with either standard or aggressive supplementation strategies.

      Single high-dose oral vitamin D therapy, known as stoss therapy, has been used in other
      chronically ill children where adequate levels of vitamin D are difficult to attain. Stoss
      therapy suggests a single high-dose followed by maintenance dosing would be adequate to
      replete and maintain vitamin D levels in chronically ill children. While it has been shown to
      be effective with no evidence of toxicity in patients with rickets and cystic fibrosis, its
      safety and efficacy has not been studied in the transplant setting. However, there is an
      urgent need to identify a modifiable factor may reduce the occurrence and/or severity of HSCT
      associated complications. The overall objective of this study is to determine the
      effectiveness of a single, high dose oral vitamin D (Stoss Therapy) followed by maintenance
      supplementation in children undergoing HSCT. This change will result in a new and innovative
      approach to maintaining adequate vitamin D levels during pediatric HSCT, with the long term
      goal of reducing morbidity and mortality.

      Our primary goal is to assess the safety and efficacy of a single, high dose of vitamin D
      followed by maintenance supplementation in children undergoing HSCT. Our secondary goal is to
      identify the effects of adequate vitamin D levels on early clinical outcomes such as cytokine
      levels, graft versus host disease, immune recovery, rejection, relapse, infection rates in
      pediatric HSCT patients.
    

Intervention name(s): Vitamin D3; Standard Vitamin D3 Supplementation
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The single, oral dose of vitamin D3 is based on patient's age and baseline 25-hydroxy-vitamin D level. Dosing is as follows: (1) For children under 3 years of age. 200000IU for those deficient, 150000IU for those insufficient, and 100000IU for those sufficient; (2) For children 3-12 years of age, 400000IU for those deficient, 350000IU for those insufficient, and 200000IU for those sufficient; (3) For children greater than 12 years of age, 600000IU for those deficient, 500000IU for those insufficient, and 300000IU for those sufficient. This is a single, one time oral dose given prior to the start of transplant.; Those who have sufficient vitamin D will be supplemented with 400-600IU/day of Vitamin D3 orally.
Those who have insufficient or are deficient in vitamin D will be supplemented with 50,000IU/week of Vitamin D3 orally.
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients enrolled in the study will be randomized to either a control or intervention arm prior to the start of transplant using block randomization of blocks of 6. Those randomized to the intervention arm will receive the intervention (Stoss Therapy dosing of vitamin D) at the start of transplant followed by maintenance supplementation of vitamin D according to standard of care. Those randomized into the control arm will receive only maintenance supplementation of vitamin D according to standard of care throughout transplant.
Masking: None (Open Label)
Primary purpose: Treatment