vorinostat and Graft vs Host Disease studies

Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).

Graft vs Host Disease: The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.

Research Excerpts

Excerpt	Relevance	Reference
"Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models."	6.79	Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. ( Beumer, JH; Braun, T; Chang, L; Choi, SW; Couriel, DR; Dinarello, CA; DiPersio, JF; Ferrara, JL; Goldstein, S; Hou, G; Kitko, C; Krijanovski, OI; Lehmann, MH; Levine, JE; Magenau, JM; Mapara, MY; Paczesny, S; Pawarode, A; Reddy, P; Stockerl-Goldstein, K; Sun, Y; Tawara, I; Yanik, GA, 2014)
"The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT)."	5.24	Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. ( Braun, T; Choi, SW; Dinarello, CA; Gatza, E; Henig, I; Magenau, J; Parkin, B; Pawarode, A; Reddy, P; Riwes, M; Yanik, G, 2017)
"We examined immunological responses in patients receiving histone deacetylase (HDAC) inhibition (vorinostat) for graft-versus-host disease prophylaxis after allogeneic hematopoietic cell transplant."	5.20	Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans. ( Choi, SW; Dinarello, CA; Gatza, E; Hou, G; Oravecz-Wilson, K; Reddy, P; Song, Y; Sun, Y; Tawara, I; Whitfield, J, 2015)
"Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models."	2.79	Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. ( Beumer, JH; Braun, T; Chang, L; Choi, SW; Couriel, DR; Dinarello, CA; DiPersio, JF; Ferrara, JL; Goldstein, S; Hou, G; Kitko, C; Krijanovski, OI; Lehmann, MH; Levine, JE; Magenau, JM; Mapara, MY; Paczesny, S; Pawarode, A; Reddy, P; Stockerl-Goldstein, K; Sun, Y; Tawara, I; Yanik, GA, 2014)

Research

Studies (12)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Non-Relapse Mortality Incidence

Percentage of Patients Alive at 1 Year

Percentage of Patients That Experience Grade 2-4 GVHD Within 100 Days of Transplant

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	3 (25.00)	29.6817
2010's	8 (66.67)	24.3611
2020's	1 (8.33)	2.80

Authors	Studies
Alatrash, G	1
Saberian, C	1
Bassett, R	1
Thall, PF	1
Ledesma, C	1
Lu, Y	1
Daher, M	1
Valdez, BC	1
Kawedia, J	1
Popat, U	1
Mehta, R	1
Oran, B	1
Nieto, Y	1
Olson, A	1
Anderlini, P	1
Marin, D	1
Hosing, C	1
Alousi, AM	1
Shpall, EJ	1
Rondon, G	1
Chen, J	1
Qazilbash, M	1
Champlin, RE	1
Kebriaei, P	1
Choi, SW	3
Braun, T	2
Henig, I	1
Gatza, E	3
Magenau, J	1
Parkin, B	1
Pawarode, A	2
Riwes, M	1
Yanik, G	1
Dinarello, CA	5
Reddy, P	6
Holtan, SG	1
Weisdorf, DJ	1
McNeil, C	1
Hancock, WW	1
Chang, L	1
Ferrara, JL	3
Magenau, JM	1
Hou, G	2
Beumer, JH	1
Levine, JE	1
Goldstein, S	1
Couriel, DR	1
Stockerl-Goldstein, K	1
Krijanovski, OI	1
Kitko, C	1
Yanik, GA	1
Lehmann, MH	1
Tawara, I	3
Sun, Y	3
Paczesny, S	1
Mapara, MY	2
DiPersio, JF	1
Whitfield, J	1
Song, Y	1
Oravecz-Wilson, K	1
Hülsdünker, J	1
Zeiser, R	1
Toubai, T	1
Duran-Struuck, R	1
Clouthier, SG	1
Weisiger, E	1
Maeda, Y	2
Krijanovski, O	1
Liu, C	2
Malter, C	1
Mascagni, P	2
de Lima, M	1
Koreth, J	1
Hotary, K	1
Reznikov, LL	1
Leng, C	1
Gries, M	1
Ziegler, J	1
Lokshin, A	1
Lentzsch, S	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Pilot Trial of Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Allogeneic Transplant[NCT01790568]	Phase 2	26 participants (Actual)	Interventional	2014-12-31	Completed
An Open-Label, Proof of Concept Study of Vorinostat for the Treatment of Moderate-to-Severe Crohn's Disease and Maintenance Therapy With Ustekinumab[NCT03167437]	Phase 1/Phase 2	35 participants (Anticipated)	Interventional	2017-10-30	Recruiting
Phase II Trial of Vorinostat Plus Tacrolimus & Mycophenolate to Prevent Graft Versus Host Disease Following Reduced Intensity Conditioning Related Donor Allogeneic Transplant[NCT00810602]	Phase 1/Phase 2	61 participants (Actual)	Interventional	2009-01-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	percentage of patients (Number)
Vorinostat	16

Intervention	percentage of patients (Number)
Vorinostat	76

"GVHD Staging:~Grade 2: (Skin) Maculopapular rash 25-50% BSA, (Liver) bilirubin 3.1-6mg/dl, (Gut) 1000-1500 ml/day for adult and 20-30ml/kg/day for child.~Grade 3: (Skin) Maculopapular rash >50% BSA, (Liver) 6.1-15mg/dl, (Gut) >1500mg/day for adult and >30ml/kg/day for child.~Grade 4: (Skin) Generalized erythroderma plus bullous formation and desquamation >5% BSA, (Liver) >15mg/dl, (Gut) Severe abdominal pain with or without ileus, or grossly bloody stool." (NCT01790568)
Timeframe: 100 Days

100-day Cumulative Incidence of Grade 2-4 Acute Graft Versus Host Disease (GVHD)

Intervention	percentage of patients (Number)
Vorinostat	22

Assess if the addition of Vorinostat to standard GVHD prophylaxis regimen can reduce the rate of grades 2-4 acute GVHD when compared to 48% in a cohort of identically treated RIC HSCT patients without vorinostat. A reduction of incidence to less than 25% will be considered successful. (NCT00810602)
Timeframe: 100 days

Number of Serious Adverse Events

Intervention	percentage of participants (Number)
Vorinostat Prophylaxis	22

The safety and feasibility will be partially measured by the number of serious adverse events (SAE) recorded by participants receiving at least one dose of Vorinostat. (NCT00810602)
Timeframe: 100 days

Percent Cumulative Incidence of Relapse at 2 Years.

Intervention	Number of Serious Adverse Events (Number)
Vorinostat Prophylaxis	33

Determine the cumulative incidence of relapse at 2 years. (NCT00810602)
Timeframe: two years

Article	Year
Insights into the pathogenesis of GvHD: what mice can teach us about man. Tissue antigens, 2015, Volume: 85, Issue:1 Topics: Adoptive Transfer; Animals; Antineoplastic Agents; Disease Models, Animal; Graft vs Host Disease; Gr	2015
Emerging therapies in hematopoietic stem cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2012, Volume: 18, Issue:1 Suppl Topics: Antineoplastic Agents; Azacitidine; Boronic Acids; Bortezomib; Graft vs Host Disease; Graft vs Tumor	2012

Article	Year
Vorinostat Combined with Busulfan, Fludarabine, and Clofarabine Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia: Long-Term Study Outcomes. Transplantation and cellular therapy, 2022, Volume: 28, Issue:8 Topics: Acute Disease; Busulfan; Clofarabine; Drug Therapy, Combination; Graft vs Host Disease; Hematopoieti	2022
Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. Blood, 2017, 10-12, Volume: 130, Issue:15 Topics: Acetylation; Acute Disease; Adolescent; Adult; Aged; Demography; Feasibility Studies; Female; Graft	2017
Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. The Lancet. Oncology, 2014, Volume: 15, Issue:1 Topics: Acute Disease; Adult; Aged; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation;	2014
Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. The Lancet. Oncology, 2014, Volume: 15, Issue:1 Topics: Acute Disease; Adult; Aged; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation;	2014
Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. The Lancet. Oncology, 2014, Volume: 15, Issue:1 Topics: Acute Disease; Adult; Aged; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation;	2014
Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. The Lancet. Oncology, 2014, Volume: 15, Issue:1 Topics: Acute Disease; Adult; Aged; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation;	2014
Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans. Blood, 2015, Jan-29, Volume: 125, Issue:5 Topics: Acetylation; Adult; Aged; Cytokines; Female; Forkhead Transcription Factors; Gene Expression Regulat	2015

Article	Year
Vorinostat is victorious in GVHD prevention. Blood, 2017, 10-12, Volume: 130, Issue:15 Topics: Graft vs Host Disease; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Vorinostat	2017
Preventing graft-versus-host disease: transplanters glimpse hope beyond immunosuppressants. Journal of the National Cancer Institute, 2013, Jul-03, Volume: 105, Issue:13 Topics: Acute Disease; Bone Marrow Transplantation; Boronic Acids; Bortezomib; Chronic Disease; Clinical Tri	2013
Effects of histone deacetylase inhibitors on alloresponses. The Lancet. Oncology, 2014, Volume: 15, Issue:1 Topics: Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histone Deacetylase Inhibito	2014
Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice. The Journal of clinical investigation, 2008, Volume: 118, Issue:7 Topics: Animals; Antigens, CD; Bone Marrow Transplantation; Cytokines; Dendritic Cells; Enzyme Inhibitors; F	2008
Histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect. Proceedings of the National Academy of Sciences of the United States of America, 2004, Mar-16, Volume: 101, Issue:11 Topics: Animals; Bone Marrow Transplantation; Cytokines; Female; Graft vs Host Disease; Histone Deacetylase	2004
Reduction of graft-versus-host disease by histone deacetylase inhibitor suberonylanilide hydroxamic acid is associated with modulation of inflammatory cytokine milieu and involves inhibition of STAT1. Experimental hematology, 2006, Volume: 34, Issue:6 Topics: Animals; Bone Marrow Transplantation; Cell Proliferation; Cytokines; Enzyme Inhibitors; Female; Graf	2006

vorinostat and Graft vs Host Disease