Clinical trial NCT02600988: Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant
Official title: Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematopoietic Stem Cell Transplantation
Keywords: Graft-Versus-Host-Disease
post-allogeneic transplant
haematopoietic progenitors
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2015-11-10
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether vitamin D is effective in the prevention of graft-versus-host-disease after completion of allogeneic transplant.

Detailed description: The allogeneic transplant of haematopoietic cell is the only treatment option for many malignant blood diseases. Unfortunately, the progression free survival and the quality of life of transplanted patients is limited due to the development of graft-versus-host-disease (GVHD).

The development of new prophylaxis strategies of GVHD based in the use of immunomodulator agents (allowing the generation of an immunotolerance state and avoiding the use of immunosuppression) is essential.

The GVHD is due to the cytotoxic effect of the donor lymphocytes T against healthy organs and tissues of the receptor. Calcineurin inhibitor combined with methotrexate or antibodies anti-lymphocytes T are used as standard prophylaxis. This type of antibodies has demonstrated efficacy to reduce GVHD, but have not increased survival due to increasing the risk of relapses and serious post-transplant infections.

Due to its interactions with VDR (vitamin D receptor) present in immune system cells, vitamin D is able to inhibit the activation of dendritic cells and the proliferation and production of cytokines by lymphocytes T. Based on this effect, the peri- and post- transplant administration of vitamin D might decrease the risk of GVHD in allogeneic transplanted patients, subsequently decreasing the immunosuppressant treatment requirements and improving the prognosis of those patients.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* The patient should accomplish all the criteria to proceed to an allogeneic transplant
* The patient or their legal guardians should signed the informed consent approved by the Ethics Committees of Clinical Trials

Exclusion Criteria:

* Hypercalcemia ≥ 10.5 mg/dl
* Renal insufficiency with creatinine level ≥ 2 x upper limit of normal (1,1 mg/dl)
* Participation in others Clinical Trials in which the intervention may affect the result of the study.
* Patients receiving GVHD immunoprophylaxis with thymoglobuline or GVHD prophylaxis including in vitro or in vivo lymphocytes T depletion (anti-lymphocyte T globulin, ALG)
* Patients receiving a transplant from an haploidentical donor

Primary outcomes:
measure: Incidence/severity of Graft-Versus-Host-Disease
timeFrame: Day +150 post-transplant
Secondary outcomes:
measure: Serum levels of Th1/Th2 cytokines
timeFrame: Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant
measure: Dendritic cells
timeFrame: Day +21,+56 and +100 post-transplant
measure: Subpopulations of lymphocytes
timeFrame: Day +21,+56 and +100 post-transplant
measure: Regulatory T cells
timeFrame: Day +21,+56 and +100 post-transplant
measure: NK markers
timeFrame: Day +21,+56 and +100 post-transplant
measure: Activation of T cells
timeFrame: Day +21,+56 and +100 post-transplant
measure: Peak Plasma Concentration (Cmax) of Vitamin D
timeFrame: Day -5 pre-transplant and +1, +7 and +21 post-transplant
measure: Area under the plasma concentration of Vitamin D
timeFrame: Day -5 pre-transplant and +1, +7 and +21 post-transplant
measure: Bone densitometry changes carried out by protocol in post-transplant period
timeFrame: Day +150 post-transplant
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Christelle Ferrà i Coll
state: Barcelona
city: Jerez de la Frontera
country: Spain
facility: Raquel Saldaña Moreno
state: Cádiz
city: Barcelona
country: Spain
facility: Carmen Martínez
city: Barcelona
country: Spain
facility: David Valcárcel Ferreiras
city: Granada
country: Spain
facility: Manuel Jurado Chacón
city: Málaga
country: Spain
facility: Mª Ángeles Cuesta
city: Salamanca
country: Spain
facility: Fermín Martín Sánchez- Guijo
Study officials:
affiliation: Head of haematology department
name: José Antonio Pérez-Simón, MD-PhD
role: STUDY_CHAIR
References:
citation: Carrillo-Cruz E, Garcia-Lozano JR, Marquez-Malaver FJ, Sanchez-Guijo FM, Montero Cuadrado I, Ferra I Coll C, Valcarcel D, Lopez-Godino O, Cuesta M, Parody R, Lopez-Corral L, Alcoceba M, Caballero-Velazquez T, Rodriguez-Gil A, Bejarano-Garcia JA, Ramos TL, Perez-Simon JA. Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms. Clin Cancer Res. 2019 Aug 1;25(15):4616-4623. doi: 10.1158/1078-0432.CCR-18-3875. Epub 2019 May 1.
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.