glycine and Graft vs Host Disease studies

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
"Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD."	6.94	Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation. ( Abedin, S; Chhabra, S; D'Souza, A; Dhakal, B; Douglas Rizzo, J; Drobyski, WR; Fenske, TS; Hamadani, M; Hari, PN; Horowitz, MM; Jerkins, JH; Pasquini, MC; Runaas, L; Saber, W; Shah, NN; Shaw, BE; Tang, X; Thompson, R; Visotcky, A; Zhang, MJ; Zhu, F, 2020)
"Ixazomib is an oral proteasome inhibitor with a wide safety profile that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, and anti-tumor activity."	5.62	Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation. ( Cho, C; Dahi, P; Devlin, SM; Flynn, L; Giralt, S; Lee, J; Murray, F; Perales, MA; Ponce, DM; Rodriguez, N; Sauter, C; Soto, C, 2021)
" We chose ixazomib, an orally bioavailable proteasome inhibitor, because of its favorable physiochemical characteristics."	5.46	Post-Transplantation Cyclophosphamide and Ixazomib Combination Rescues Mice Subjected to Experimental Graft-versus-Host Disease and Is Superior to Either Agent Alone. ( Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)
"Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate."	5.46	Ixazomib suppresses human dendritic cell and modulates murine graft-versus-host disease in a schedule-dependent fashion. ( Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)
" We performed a phase 2 study that examined the effects of ixazomib for graft-versus-host disease (GVHD) prophylaxis (up to 12 cycles) with posttransplant cyclophosphamide and tacrolimus after standard nonmyeloablative haploidentical donor transplantation (HIDT)."	5.34	Prospective phase 2 trial of ixazomib after nonmyeloablative haploidentical peripheral blood stem cell transplant. ( Bashey, A; Brown, S; Holland, HK; Jackson, KC; Morris, LE; Solh, M; Solomon, SR; Zhang, X, 2020)
"Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD."	2.94	Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation. ( Abedin, S; Chhabra, S; D'Souza, A; Dhakal, B; Douglas Rizzo, J; Drobyski, WR; Fenske, TS; Hamadani, M; Hari, PN; Horowitz, MM; Jerkins, JH; Pasquini, MC; Runaas, L; Saber, W; Shah, NN; Shaw, BE; Tang, X; Thompson, R; Visotcky, A; Zhang, MJ; Zhu, F, 2020)
"Ixazomib is an oral proteasome inhibitor with a wide safety profile that has demonstrated immunomodulatory properties, inhibition of pro-inflammatory cytokines, and anti-tumor activity."	1.62	Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation. ( Cho, C; Dahi, P; Devlin, SM; Flynn, L; Giralt, S; Lee, J; Murray, F; Perales, MA; Ponce, DM; Rodriguez, N; Sauter, C; Soto, C, 2021)
" We chose ixazomib, an orally bioavailable proteasome inhibitor, because of its favorable physiochemical characteristics."	1.46	Post-Transplantation Cyclophosphamide and Ixazomib Combination Rescues Mice Subjected to Experimental Graft-versus-Host Disease and Is Superior to Either Agent Alone. ( Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)
"Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate."	1.46	Ixazomib suppresses human dendritic cell and modulates murine graft-versus-host disease in a schedule-dependent fashion. ( Abdel-Mageed, S; Al-Homsi, AS; Cole, K; Feng, Y; Goodyke, A; McLane, M; Muilenburg, M, 2017)

Research

Studies (13)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Cumulative Incidence of Chronic Graft-versus-host Disease.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	5 (38.46)	18.2507
2000's	1 (7.69)	29.6817
2010's	2 (15.38)	24.3611
2020's	5 (38.46)	2.80

Authors	Studies
Ramos, TL	1
García-Guerrero, E	1
Caballero-Velázquez, T	1
Rodríguez-Gil, A	1
Caracuel-García, R	1
Nufer, M	1
Robles-Frías, MJ	1
Barbado, MV	1
Pérez-Simón, JA	1
Pidala, J	1
Bhatt, VR	1
Hamilton, B	1
Pusic, I	1
Wood, WA	1
Onstad, L	1
Hall, AM	1
Storer, B	1
Lee, SJ	1
Chhabra, S	1
Visotcky, A	1
Pasquini, MC	1
Zhu, F	1
Tang, X	1
Zhang, MJ	1
Thompson, R	1
Abedin, S	1
D'Souza, A	1
Dhakal, B	1
Drobyski, WR	1
Fenske, TS	1
Jerkins, JH	1
Douglas Rizzo, J	1
Runaas, L	1
Saber, W	1
Shah, NN	1
Shaw, BE	1
Horowitz, MM	1
Hari, PN	1
Hamadani, M	1
Solomon, SR	1
Solh, M	1
Zhang, X	1
Brown, S	1
Jackson, KC	1
Holland, HK	1
Morris, LE	1
Bashey, A	1
Rodriguez, N	1
Lee, J	1
Flynn, L	1
Murray, F	1
Devlin, SM	1
Soto, C	1
Cho, C	1
Dahi, P	1
Giralt, S	1
Perales, MA	1
Sauter, C	1
Ponce, DM	1
Al-Homsi, AS	2
Goodyke, A	2
McLane, M	2
Abdel-Mageed, S	2
Cole, K	2
Muilenburg, M	2
Feng, Y	2
de Giorgi, L	1
Arrigoni-Martelli, E	1
Matossian-Rogers, A	1
Hattori, K	4
Hirano, T	4
Ushiyama, C	2
Miyajima, H	3
Yamakawa, N	3
Ebata, T	1
Wada, Y	1
Ikeda, S	3
Yoshino, K	3
Tateno, M	3
Oshimi, K	4
Kayagaki, N	3
Yagita, H	4
Okumura, K	4
Lebreton, L	1
Annat, J	1
Derrepas, P	1
Dutartre, P	1
Renaut, P	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
MLN9708 for the Prophylaxis of Chronic Graft-versus-host Disease in Patient Undergoing Allogeneic Transplantation[NCT02250300]	Phase 1/Phase 2	68 participants (Actual)	Interventional	2014-11-19	Completed
A Phase II Trial of Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation Followed By Maintenance Therapy With the Novel Oral Proteasome Inhibitor, MLN9708, in Patients With High-risk Hematologic Malignancies[NCT02169791]	Phase 2	29 participants (Actual)	Interventional	2014-07-15	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The number of participants who have graft-versus-host disease. The two expansion phase cohorts (3.0 mg and 4.0 mg) were not included in this analysis. (NCT02250300)
Timeframe: 1 year

Maximum-tolerated Dose of MLN9708.

Intervention	Participants (Count of Participants)
MLN9708 Phase II Matched Sibling	9
MLN9708 Phase II Matched Unrelated	10

Maximum-tolerated dose of ixazomib (MLN9708) will be determined from the incidence of dose limiting toxicities at each dosage. Results for both escalation phase cohorts (3.0 mg and 4.0 mg) were used to determine the maximum tolerated dose. (NCT02250300)
Timeframe: 4 weeks

Number of Participants Experiencing Dose-limiting Toxicity of MLN9708

Intervention	millligram (Number)
Maximum Tolerated Dose of Study Drug	4

A 3+3 design will be employed. At each dose, three patients will be initially evaluated. If no dose limiting toxicities are observed, the MLN9708 dose will be increased; if one dose limiting toxicity is observed, three additional patients will be treated at that dose. A dose at which two DLTs are observed in three or six patients are judged to be too toxic, the lower dose will be defined as the maximally tolerated dose (MTD). (NCT02250300)
Timeframe: 4 weeks

Day 30 CD3 Donor Chimerism

Day 30 CD33 Donor Chimerism

Graft Versus Host Disease

Intervention	dose limiting toxicity (Number)
MLN9708 Phase I (3.0 mg)	0
MLN9708 Phase I (4.0 mg)	0

Intervention	percentage of chimerism (Median)
Haploidentical Transplant	100

Intervention	percentage of chimerism (Median)
Haploidentical Transplant	100

To measure days to onset of acute graft versus host disease (NCT02169791)
Timeframe: 100 days

Neutrophil Engraftment

Intervention	days (Median)
Haploidentical Transplant	28.5

To obtain time to neutrophil engraftment post-transplant (NCT02169791)
Timeframe: 1 year

Number of Participants Experiencing Relapse or Progression

Intervention	days (Median)
Haploidentical Transplant	16

To estimate the incidence of relapse/progression at one-year post-transplant. (NCT02169791)
Timeframe: 1 year

Time to Platelet Recovery Post Transplant

Intervention	Participants (Count of Participants)
Haploidentical Transplant	10

To measure the time to platelet recovery post-transplant (NCT02169791)
Timeframe: 1 year

Article	Year
Ixazomib for Treatment of Refractory Chronic Graft-versus-Host Disease: A Chronic GVHD Consortium Phase II Trial. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2020, Volume: 26, Issue:9 Topics: Boron Compounds; Chronic Disease; Glycine; Graft vs Host Disease; Hematopoietic Stem Cell Transplant	2020
Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2020, Volume: 26, Issue:10 Topics: Boron Compounds; Chronic Disease; Glycine; Graft vs Host Disease; Hematopoietic Stem Cell Transplant	2020
Prospective phase 2 trial of ixazomib after nonmyeloablative haploidentical peripheral blood stem cell transplant. Blood advances, 2020, 08-11, Volume: 4, Issue:15 Topics: Adult; Aged; Boron Compounds; Glycine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantatio	2020

Article	Year
Delayed administration of ixazomib modifies the immune response and prevents chronic graft-versus-host disease. Bone marrow transplantation, 2021, Volume: 56, Issue:12 Topics: Animals; Bone Marrow Transplantation; Boron Compounds; Glycine; Graft vs Host Disease; Graft vs Leuk	2021
Oral Proteasome Inhibitor Ixazomib for Switch-Maintenance Prophylaxis of Recurrent or Late Acute and Chronic Graft-versus-Host Disease after Day 100 in Allogeneic Stem Cell Transplantation. Transplantation and cellular therapy, 2021, Volume: 27, Issue:11 Topics: Boron Compounds; Glycine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Ne	2021
Post-Transplantation Cyclophosphamide and Ixazomib Combination Rescues Mice Subjected to Experimental Graft-versus-Host Disease and Is Superior to Either Agent Alone. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017, Volume: 23, Issue:2 Topics: Animals; Bone Marrow Transplantation; Boron Compounds; Cyclophosphamide; Cytokines; Drug Administrat	2017
Ixazomib suppresses human dendritic cell and modulates murine graft-versus-host disease in a schedule-dependent fashion. Experimental hematology, 2017, Volume: 48 Topics: Animals; Boron Compounds; Cell Differentiation; Cytokines; Dendritic Cells; Disease Models, Animal;	2017
Immunosuppressive effect of stepronin (TS-5010680) in mice. Transplantation proceedings, 1994, Volume: 26, Issue:6 Topics: Animals; Cells, Cultured; Concanavalin A; Glycine; Graft vs Host Disease; Immunosuppressive Agents;	1994
A metalloproteinase inhibitor prevents lethal acute graft-versus-host disease in mice. Blood, 1997, Jul-15, Volume: 90, Issue:2 Topics: Animals; Crosses, Genetic; Fas Ligand Protein; Female; Glycine; Graft vs Host Disease; Humans; Hydro	1997
Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety. Journal of medicinal chemistry, 1999, Jan-28, Volume: 42, Issue:2 Topics: Animals; Glycine; Graft vs Host Disease; Guanidines; Heart Transplantation; Immunosuppressive Agents	1999
A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation. British journal of haematology, 1999, Volume: 105, Issue:1 Topics: Animals; Bone Marrow Transplantation; Female; Flow Cytometry; Glycine; Graft vs Host Disease; Graft	1999
A metalloproteinase inhibitor prevents acute graft-versus-host disease in mice after bone marrow transplantation. Bone marrow transplantation, 1999, Volume: 23, Issue:12 Topics: Animals; Bone Marrow Transplantation; Cell Separation; Female; Flow Cytometry; Glycine; Graft vs Hos	1999
A metalloproteinase inhibitor prevents acute graft-versus-host disease while preserving the graft-versus-leukaemia effect of allogeneic bone marrow transplantation. Leukemia & lymphoma, 2000, Volume: 38, Issue:5-6 Topics: Animals; B-Lymphocytes; Bone Marrow Transplantation; Fas Ligand Protein; Glycine; Graft vs Host Dise	2000

glycine and Graft vs Host Disease