Rituximab for the Primary Treatment of Denovo Extensive Chronic Graft Versus Host Disease (GVHD)

NCT01161628 | Completed Phase 2 Results

• 1 other identifier: NSH 893
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Rituximab is an attractive agent to bring to the upfront treatment of chronic graft-versus-host disease (cGVHD) due to its favorable toxicity profile, its proven efficacy in the treatment of steroid-refractory cGVHD, and its ability to serve as a steroid sparing agent in other autoimmune diseases. The investigators hope to demonstrate that Rituximab has significant activity in cGVHD when utilized early in the course of the process. In addition, the investigators hope to show that the early use of Rituximab may allow for the earlier discontinuation of immunosuppression while obviating the need for long courses of systemic corticosteroids, which should translate into reduced treatment-related morbidity and mortality associated with cGVHD.

Conditions

Chronic Graft-versus-host Disease

Keywords

Chronic Graft versus Host Disease; allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (3)

• Rate of Complete Response of cGVHD to Treatment.

  2 years

• Rate of Overall Response of cGVHD to Treatment

  2 years

• Rate of Partial Response of cGVHD to Treatment

  2 years

Secondary Outcomes (6)

• Requirement for Systemic Corticosteroid Use

  2 years

• Time to Immunosuppression Withdrawal

  2 years

• Incidence of Overall Survival

  2 years

• Duration of Systemic Corticosteroid Use

  2 years

• Incidence of Disease-free Survival

  2 years

Study Arms (1)

Rituxan

EXPERIMENTAL

All patients receive Rituximab 375 mg/m2/dose x 4 weekly doses on days 1, 8, 15 and 22 and then at 3, 6, 9 and 12 months.

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab 375 mg/m2/dose x 4 weekly doses on days 1, 8, 15 and 22 and then at 3, 6, 9 and 12 months.

Also known as: Rituxan

Rituxan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First episode of extensive chronic GvHD, without residual or concurrent acute GvHD.
• Age 18 - 75
• Any primary diagnosis requiring treatment by allogeneic HSCT
• Recipient of an allogeneic stem cell transplant (bone marrow, peripheral blood stem cell, or cord blood) from a related or unrelated donor, minimum 80 days ago
• Conditioning regimen: Myeloablative or non-myeloablative
• Patient gives written informed consent

You may not qualify if:

• Creatinine \> 2.0 mg/dl
• Uncontrolled, active infection
• Recurrent or progressive malignancy
• Anticipated life expectancy of less than 1 year
• Pregnant or breast feeding
• Contraindications to administration of the study intervention or known inability of the patient to tolerate the study intervention
• Patients with perceived fixed, irreversible defects (pulmonary involvement, contractures, etc.) which would not be expected to improve with the study intervention
• Residual or concurrent acute GVHD

Sponsors & Collaborators

• Northside Hospital, Inc.: lead
• Blood and Marrow Transplant Group of Georgia: collaborator

Study Sites (1)

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Related Publications (8)

• Canninga-van Dijk MR, van der Straaten HM, Fijnheer R, Sanders CJ, van den Tweel JG, Verdonck LF. Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease. Blood. 2004 Oct 15;104(8):2603-6. doi: 10.1182/blood-2004-05-1855. Epub 2004 Jul 13.

  PMID: 15251978 BACKGROUND

• Ratanatharathorn V, Carson E, Reynolds C, Ayash LJ, Levine J, Yanik G, Silver SM, Ferrara JL, Uberti JP. Anti-CD20 chimeric monoclonal antibody treatment of refractory immune-mediated thrombocytopenia in a patient with chronic graft-versus-host disease. Ann Intern Med. 2000 Aug 15;133(4):275-9. doi: 10.7326/0003-4819-133-4-200008150-00011.

  PMID: 10929168 BACKGROUND

• Ratanatharathorn V, Ayash L, Reynolds C, Silver S, Reddy P, Becker M, Ferrara JL, Uberti JP. Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody. Biol Blood Marrow Transplant. 2003 Aug;9(8):505-11. doi: 10.1016/s1083-8791(03)00216-7.

  PMID: 12931119 BACKGROUND

• Okamoto M, Okano A, Akamatsu S, Ashihara E, Inaba T, Takenaka H, Katoh N, Kishimoto S, Shimazaki C. Rituximab is effective for steroid-refractory sclerodermatous chronic graft-versus-host disease. Leukemia. 2006 Jan;20(1):172-3. doi: 10.1038/sj.leu.2403996. No abstract available.

  PMID: 16239908 BACKGROUND

• Zaja F, Bacigalupo A, Patriarca F, Stanzani M, Van Lint MT, Fili C, Scime R, Milone G, Falda M, Vener C, Laszlo D, Alessandrino PE, Narni F, Sica S, Olivieri A, Sperotto A, Bosi A, Bonifazi F, Fanin R; GITMO (Gruppo Italiano Trapianto Midollo Osseo). Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant. 2007 Aug;40(3):273-7. doi: 10.1038/sj.bmt.1705725. Epub 2007 Jun 4.

  PMID: 17549053 BACKGROUND

• Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood. 2006 Jul 15;108(2):756-62. doi: 10.1182/blood-2006-01-0233. Epub 2006 Mar 21.

  PMID: 16551963 BACKGROUND

• Stewart BL, Storer B, Storek J, Deeg HJ, Storb R, Hansen JA, Appelbaum FR, Carpenter PA, Sanders JE, Kiem HP, Nash RA, Petersdorf EW, Moravec C, Morton AJ, Anasetti C, Flowers ME, Martin PJ. Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood. 2004 Dec 1;104(12):3501-6. doi: 10.1182/blood-2004-01-0200. Epub 2004 Aug 3.

  PMID: 15292060 BACKGROUND

• Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003 Apr;9(4):215-33. doi: 10.1053/bbmt.2003.50026.

  PMID: 12720215 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Scott R. Solomon, MD (Principal Investigator)
• Organization: Blood and Marrow Transplant Group of Georgia

ssolomon@bmtga.com

404-255-1930

Study Officials

• Scott R Solomon, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 13, 2010
• Study Start: April 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: July 1, 2015
• Last Updated: April 20, 2016
• Results First Posted: February 24, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)