Clinical trial NCT03759262: Ultra-high Dose Vitamin D for HSCT
Official title: Pilot Study of Transplant-related Events in Patients Receiving Ultra-high-dose Vitamin D Supplementation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematopoietic Stem Cell Transplant
Keywords: vitamin D
cytokines
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
First posted: 2018-11-29
Enrollment: 33
Sex: ALL
Minimum age (years): 0
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of graft-versus-host disease, veno-occlusive disease, and thrombotic microangiopathy
timeFrame: 100 days after transplant
measure: Vitamin D sufficiency following Stoss dosing
timeFrame: prior to transplant
Secondary outcomes:
measure: Rates of survival, relapse, and significant infections
timeFrame: from time of transplant to 1 year after transplant
measure: Cytokine levels
timeFrame: before vitamin D is given, 1-2 weeks after vitamin D is given, day of transplant, day +7, day +14, and day +30
measure: Cytokine stimulation test
timeFrame: before vitamin D is given, and 1-2 weeks after vitamin D is given
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
Study officials:
affiliation: Children's Hospital Los Angeles
name: Etan Orgel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wallace G, Jodele S, Howell J, Myers KC, Teusink A, Zhao X, Setchell K, Holtzapfel C, Lane A, Taggart C, Laskin BL, Davies SM. Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2015 Sep;21(9):1627-31. doi: 10.1016/j.bbmt.2015.06.009. Epub 2015 Jun 18.
citation: Wallace G, Jodele S, Myers KC, Dandoy CE, El-Bietar J, Nelson A, Teusink-Cross A, Khandelwal P, Taggart C, Gordon CM, Davies SM, Howell JC. Single Ultra-High-Dose Cholecalciferol to Prevent Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018 Sep;24(9):1856-1860. doi: 10.1016/j.bbmt.2018.05.019. Epub 2018 May 18.
citation: Hansson ME, Norlin AC, Omazic B, Wikstrom AC, Bergman P, Winiarski J, Remberger M, Sundin M. Vitamin d levels affect outcome in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Oct;20(10):1537-43. doi: 10.1016/j.bbmt.2014.05.030. Epub 2014 Jun 5.
citation: Caballero-Velazquez T, Montero I, Sanchez-Guijo F, Parody R, Saldana R, Valcarcel D, Lopez-Godino O, Ferra I Coll C, Cuesta M, Carrillo-Vico A, Sanchez-Abarca LI, Lopez-Corral L, Marquez-Malaver FJ, Perez-Simon JA; GETH (Grupo Espanol de Trasplante Hematopoyetico). Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial. Clin Cancer Res. 2016 Dec 1;22(23):5673-5681. doi: 10.1158/1078-0432.CCR-16-0238. Epub 2016 Jun 29.
citation: van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):93-101. doi: 10.1016/j.jsbmb.2005.06.002. Epub 2005 Jul 19.