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Hematopoietic Stem Cell TransplantationPhase 1/2Alovita-1NCT02600988

Immunomodulatory Effect of Vitamin D in Allogenic Post-transplant

A Phase 1/2 study testing 1000IU/day of Vitamine D and 5000IU/day of Vitamine D in people with Hematopoietic Stem Cell Transplantation, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 7 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hematopoietic Stem Cell Transplantation
What is being tested?
1000IU/day of Vitamine D and 5000IU/day of Vitamine D
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
7 sitesSpain
Study dates
Jul 2011to Apr 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Spain7 sites

  • Christelle Ferrà i Coll

    Badalona, Barcelona

  • Carmen Martínez

    Barcelona, Barcelona

  • David Valcárcel Ferreiras

    Barcelona, Barcelona

  • Manuel Jurado Chacón

    Granada, Granada

  • Raquel Saldaña Moreno

    Jerez de la Frontera, Cádiz

  • Mª Ángeles Cuesta

    Málaga, Málaga

  • Fermín Martín Sánchez- Guijo

    Salamanca, Salamanca

Other trials in Spain

About this study

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.

Read the 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.

Being tested
1000IU/day of Vitamine D, 5000IU/day of Vitamine D
Keywords
Graft-Versus-Host-Disease, post-allogeneic transplant, haematopoietic progenitors
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 1000IU/day of Vitamine DDrug

    Also called Vitamine D dose of 1000 international units (IU)

    Administration of a specified dose of Vitamine D

  • 5000IU/day of Vitamine DDrug

    Also called Vitamine D dose of 5000 international units (IU)

    Administration of a specified dose of Vitamine D

Study groups in NCT02600988
Study groupRoleWhat they receive
Group 1: ControlNo interventionControl group is composed by the first 50 patients included in the study. Those patients will not receive the treatment. Evaluations and follow-up will be the same as in the other groups.
Group 2: 1000IU/day of Vitamine DExperimentalIt is composed by the following 50 patients joining the study. They will take 1000 IU of vitamin D once a day.
Receives: Drug: 1000IU/day of Vitamine D
Group 3: 5000IU/day of Vitamine DExperimentalIt is composed by the last 50 patients joining the study. They will take 5000 IU of vitamin D once a day.
Receives: Drug: 5000IU/day of Vitamine D

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence/severity of Graft-Versus-Host-Disease

    Number of cases of GVHD/Seriousness graded according to National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

    Measured: Day +150 post-transplant

Secondary outcomes (9)

  1. Serum levels of Th1/Th2 cytokines

    (IL-2, IL-4, IL-6, IL-10, tumor necrosis factor alfa (TNF)-α and interferon gamma (IFN-g)) are determined by flow cytometry using the BD Human Th1/Th2 Cytokine CBA

    Measured: Day -5 pre-transplant and +1, +7, +21,+56 and +100 post-transplant

  2. Dendritic cells

    The following markers were used to identify different subpopulations

    CD16-PB, CD45-V500, HLADR-FITC, BDCA-PE, CD11c-PerCP-Cy5.5, CD86-PE-Cy7, CD123-APC and CD14-APC-H7.

    Plasmacytoid dendritic cells: HLADR+ CD123++ CD11c- CD16- CD14- BDCA1- CD45+.

    Monocyte-derived dendritic cells: HLADR+ CD123+d CD11c+ CD16++ CD14-/+d BDCA- CD45+.

    Myeloid BDCA1 dendritic cells : HLADR+ CD123- CD11c+ CD16- CD14- BDCA+ CD45+

    Measured: Day +21,+56 and +100 post-transplant

  3. Subpopulations of lymphocytes

    To be identified using the combination CD19+CD8-FITC, CD3+CD56-PE, CD4- PerCP-Cy5.5, HLADR-APC T cells: CD3+ (CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD8+, CD3+CD4-CD8+)

    B cells: CD19+ HLADR+

    NK cells: CD3- CD19- CD56+

    CD45RA-FITC and CCR7-PE were used to distinguish the repertory of naive/effector/memory of CD4 and CD8 cells.

    -naive T cells: CD45RA+CCR7+

    -effector T cells: CD45RA+CCR7-

    -central memory T cells: CD45RA-CCR7+

    -Peripheral memory T cells: CD45RA-CCR7-

    Measured: Day +21,+56 and +100 post-transplant

  4. Regulatory T cells

    after incubation of surface antigens (CD25-FITC, CD127-PE and CD4-PerCP-Cy5.5), cells were washed in PBS and then fixed and permeabilized with FoxP3 Staining Buffer Set (eBiosciences) for FOXP3 staining.

    phenotype of Treg: CD4+CD25+CD127-/+wFoxP3+

    Measured: Day +21,+56 and +100 post-transplant

  5. NK markers

    using the following combinations:

    CD94-FITC/CD56-PE/CD3-PerCP-Cy5.5/HLADR-APC

    CD11a-FITC/CD16-PE/CD3-PerCP-Cy5.5/CD56-APC

    CD158a-FITC/CD161-PE/CD3-PerCP-Cy5.5/CD56-APC

    CDNKB1-FITC/NKAT-PE/CD3-PerCP-Cy5.5/CD56-APC

    We identify NK cells with weak expression of CD56 (CD56 called " weak) and those expressing more intensely this marker CD56 "bright ". In addition the expression of different KIR receptor as CD158a , CD161 , and NKAT2 NKB1 were reported.

    Measured: Day +21,+56 and +100 post-transplant

  6. Activation of T cells

    Activation assays are performed on 500 µl of peripheral blood added in 48-well plates. Peripheral blood is stimulated or not with PMA (20µg/2ml) and ionomycin (0.91 µg/ml).

    Measured: Day +21,+56 and +100 post-transplant

  7. Peak Plasma Concentration (Cmax) of Vitamin D

    Peak Plasma Concentration (Cmax)

    Measured: Day -5 pre-transplant and +1, +7 and +21 post-transplant

  8. Area under the plasma concentration of Vitamin D

    Area under the plasma concentration versus time curve (AUC)

    Measured: Day -5 pre-transplant and +1, +7 and +21 post-transplant

  9. Bone densitometry changes carried out by protocol in post-transplant period

    Treatment effect in the subsequent development of osteoporosis

    Measured: Day +150 post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2015 (estimated)
  2. Study startJul 2011
  3. Primary completionApr 2015
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02600988
Sponsor's protocol ID
Alovita-1
Acronym
Alovita-1
Status last verified
Nov 2015
First submitted
9 Jun 2015
Last updated
10 Nov 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 31043390

  • 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.

    PubMed 27358490

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 1000IU/day of Vitamine D and 5000IU/day of Vitamine D in people with Hematopoietic Stem Cell Transplantation, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 7 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence/severity of Graft-Versus-Host-Disease (time frame: Day +150 post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02600988, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2015.

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