Clinical Implications of HMGB1 in Patients Treated With Chemotherapy or Hematopoietic Stem Cell Transplantation

Acute Graft-versus-host Disease Clinical Trial

— CHIP-SCT  

Official title:

Observational Study for Clinical Implications of HMGB1 (High-mobility Group Protein B1) in Patients Treated With Chemotherapy or Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02044185
• Other study ID #: CMC-SGC-Lymphoma-LAB-01
• Status: Recruiting
• Phase: N/A
• First received: January 21, 2014
• Last updated: April 21, 2015
• Start date: January 2014
• Est. completion date: December 2015

Study information

• Verified date: April 2015
• Source: Seoul St. Mary's Hospital
• Contact: young-woo JEON, bachelor, MD
• Phone: 821042324067
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Acute Graft-versus-host disease(aGVDH) after allogeneic hematopoietic stem cell transplantation is one of the meaningful issues in aspect of patient's recovery and survival. in recent years, the understanding of the pathology of GVHD is much important to prevent or treat aGVHD. additionally, (oral) mucositis is one of the problems in patients with high dose chemotherapy, and mucositis by high-dose chemotherapy is related to HMGB-1 as proinflamtory cytokines. HMGB1 is a nuclear protein acts as a transcription factor, but, if it was released to the outside of cells by damaged cell or necrotic tissues, it works as cytokines for promoter of inflammation and cancers. at this point, there are no reported articles about correlation of HMGB1 and aGVHD in human. recently, we have seen excessive secretion of serum HMGB1 in mouse model, then base on this results, we will check correlation of HMGB1 and aGVHD/ oral mucositis in human.

Description:

1. materials 1) inclusion criteria

1. over 18-year-old

2. patients with myeloablative conditioning regimen

3. autologous transplant

4. patients with confirmation of acute GVHD as over grade II

5. patients with salvage chemotherapy

2) exclusion criteria

1. old age ( over 60-year-old)

2. patients with reduced intensity stem cell transplantation

2. method 1) check the serum level of HMGB1, TNF-a, IL-1b, IL-6, Th1, Th2, Th17, FoxP3 on 7-day before transplant day(D-7), transplant day(D0), 7-day after transplant(D+7), D+14, D+21. 2) check the immunohistochemistry level of tissue in diagnosed aGVHD ( performed sigmoidoscopy and random biopsy of gut is routine process in our center) 3) check the oral mucositis grades (using WHO grading system, NCI -CTC ver.3 scoring system)

3. analysis 1) student t-test , chi-square test 2) survival analysis

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

1. Inclusion Criteria:

1. over 18-year-old

2. patients with myeloablative conditioning regimen

3. autologous transplant

4. patients with confirmation of acute GVHD as over grade II

5. patients with salvage chemotherapy

2. Exclusion Criteria:

1. very old age ( over 75-year-old)

2. patients with reduced intensity stem cell transplantation

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acute Graft-versus-host Disease
• Graft vs Host Disease

Intervention

Drug:
• salvage chemotherapy, total body irradiation
there are no direct interventions to our patients.

Locations

Country	Name	City	State
Korea, Republic of	Seoul St.Mary's hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul St. Mary's Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

Brennan TV, Lin L, Huang X, Cardona DM, Li Z, Dredge K, Chao NJ, Yang Y. Heparan sulfate, an endogenous TLR4 agonist, promotes acute GVHD after allogeneic stem cell transplantation. Blood. 2012 Oct 4;120(14):2899-908. doi: 10.1182/blood-2011-07-368720. Epub 2012 Jul 3. — View Citation

Jube S, Rivera ZS, Bianchi ME, Powers A, Wang E, Pagano I, Pass HI, Gaudino G, Carbone M, Yang H. Cancer cell secretion of the DAMP protein HMGB1 supports progression in malignant mesothelioma. Cancer Res. 2012 Jul 1;72(13):3290-301. doi: 10.1158/0008-5472.CAN-11-3481. Epub 2012 May 2. — View Citation

Kang R, Zhang Q, Zeh HJ 3rd, Lotze MT, Tang D. HMGB1 in cancer: good, bad, or both? Clin Cancer Res. 2013 Aug 1;19(15):4046-57. doi: 10.1158/1078-0432.CCR-13-0495. Epub 2013 May 30. Review. — View Citation

Kornblit B, Masmas T, Petersen SL, Madsen HO, Heilmann C, Schejbel L, Sengeløv H, Müller K, Garred P, Vindeløv L. Association of HMGB1 polymorphisms with outcome after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010 Feb;16(2):239-52. doi: 10.1016/j.bbmt.2009.10.002. Epub 2009 Oct 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	tissue IHC stain level of biopsy samples of diagnosed acute GVHD		if patients diagnosed with acute GVHD will be performed random biopy of colon or stomach.	Yes
Other	oral mucositis	find-out the correlation HMGB1 level and oral mucositis grading	1 month	Yes
Primary	comparison of serum HMGB1 level before and after diagnosed acute GVHD	day 7 before stem cell transplantation(SCT), day 0, day 7, 14 after SCT, and date of diagnosed acute GVHD in all patients.	6 months	Yes
Secondary	serum level of immunosuppressive drugs in patients with acute GVHD	day 7 before stem cell transplantation(SCT), day 0, day 7, 14 after SCT, and date of diagnosed acute GVHD in all patients.	3 months	No