Ultra-high Dose Vitamin D for HSCT

Hematopoietic Stem Cell Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03759262
• Other study ID #: CHLA-18-00362
• Status: Completed
• Phase: N/A
• Start date: December 10, 2018
• Est. completion date: May 10, 2020

Study information

• Verified date: June 2020
• Source: Children's Hospital Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 10, 2020
• Est. primary completion date: May 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 25 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplant

Intervention

Drug:
• Cholecalciferol
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.

Locations

Country	Name	City	State
United States	Children's Hospital Los Angeles	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (5)

Caballero-Velázquez T, Montero I, Sánchez-Guijo F, Parody R, Saldaña R, Valcarcel D, López-Godino O, Ferra I Coll C, Cuesta M, Carrillo-Vico A, Sánchez-Abarca LI, López-Corral L, Márquez-Malaver FJ, Pérez-Simón JA; GETH (Grupo Español de Trasplante Hematopoyético). 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. Epub 2016 Jun 29. — View Citation

Hansson ME, Norlin AC, Omazic B, Wikström 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. — View 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. Epub 2005 Jul 19. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Vitamin D sufficiency following Stoss dosing	Vitamin D sufficiency following Stoss dosing prior to tranpslantation	prior to transplant
Secondary	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
Secondary	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
Secondary	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