Ultra-high Dose Vitamin D for HSCT

Study Overview
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Brief Summary
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This is a pilot study to investigate the effects of achieving adequate vitamin D levels via ultra-high-dose vitamin D supplementation given prior to hematopoietic stem cell transplant on transplant-related complications and inflammatory biomarkers.

Detailed Description
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Up to 70% of patients have vitamin D deficiency prior to hematopoietic stem cell transplant (HSCT). Patients with sufficient Vitamin D levels (>50nm/L) prior to allogeneic transplant have significantly better overall survival (OS) and lower rates of rejection and relapse. Vitamin D inhibits Th1 and augments Th2 cell development. Patients who receive vitamin D supplementation during allogeneic transplant have less inflammatory-mediated processes such as chronic graft versus host disease (GVHD) and lower levels of naïve CD8+ cells and CD40 ligand. Multiple studies have raised concern regarding the adequacy of standard and high-dose vitamin D dosing for vitamin D deficiency. A single oral ultra-high dose of Vitamin D given prior to HSCT has been shown to be a safe and well tolerated method of sustaining therapeutic Vitamin D levels for 6-19 weeks. This is a pilot study to investigate the dynamic changes in inflammatory biomarkers following ultra-high-dose vitamin D supplementation. The study population is patients with total vitamin D level </=50ng/mL prior to HSCT.

Official Title
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Pilot Study of Transplant-related Events in Patients Receiving Ultra-high-dose Vitamin D Supplementation

Conditions
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Hematopoietic Stem Cell Transplant

Intervention / Treatment
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* Drug: Cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are preparing for HSCT If a patient is receiving an autologous transplant, enrollment must occur prior to first transplant in the case that the patient is planned for multiple transplants Exclusion Criteria: Uncorrected hypocalcemia or hypophosphatemia Patients in the ICU or on renal replacement therapy Patients who have had an allogeneic transplant within the past 12 months prior to enrollment Enrolled patients with 25OHD level ≤50 ng/mL continue on study

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D (Cholecalciferol)<br>All subjects will be enrolled to this arm. A single dose of ultra-high-dose vitamin D will be given. | Drug: Cholecalciferol<br>* A single dose of ultra-high-dose vitamin D (cholecalciferol) will be given prior to hematopoietic stem cell transplant. Research labs including inflammatory biomarker panels will be obtained prior to and after the dose is given.<br>* Other names: vitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy | Graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy | 100 days after transplant | 
| Vitamin D sufficiency following Stoss dosing | Vitamin D sufficiency following Stoss dosing prior to tranpslantation | prior to transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of survival, relapse, and significant infections | Clinically significant events including but not limited to survival, relapse, significant infections. | from time of transplant to 1 year after transplant | 
| Cytokine levels | The investigators will examine changes in levels of IFN-gamma, TNF-alpha, IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 (in pg/mL) before and after vitamin D is given | before vitamin D is given, 1-2 weeks after vitamin D is given, day of transplant, day +7, day +14, and day +30 | 
| Cytokine stimulation test | The investigators will examine changes in the immune profile (reactivity of CD45, 235, 61, 66 197, 19, 4, 38, 163, 43, 7, 62L, 127, 123, 279, 274, 14, 90, 11c, 294, 15, 16, 25, 27, 8, 33, 3, 45RA, 56, 11b; pS6, p-p38, HLA-DR, pERK 1/2, pStat3, pStat1, TCRgd, pStat5) in response to cytokine stimulation before and after vitamin D is given | before vitamin D is given, and 1-2 weeks after vitamin D is given | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, cytokines