NCT00578591

Rituximab for GVHD

CHIMERIC MONOCLONAL CD-20 ANTIBODY (RITUXIMAB) FOR STEROID REFRACTORY ACUTE GRAFT VERSUS HOST DISEASE (SR-AGVHD): A PILOT STUDY

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Baylor College of Medicine · Academic / Other
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, open-label pilot study in which 4 doses of Rituximab are administered to patients who have developed SR-aGVHD following allogeneic hematopoietic transplant (AHT). The study is designed to determine the overall survival at 180 days after treatment with rituximab, and evaluates the safety and clinical response to rituximab in this study population. Study entry: Patients must enter study on or before day +100 posttransplant.

Detailed description

Acute graft-versus-host disease (aGVHD), one of the most important complications of allogeneic hematopoietic stem cell transplantation (HSCT) is associated with significant morbidity and mortality. Grades II to IV aGVHD occur in 30% to 50% of matched related donor recipients and 50% to 70% of unrelated donor recipients. Standard first-line treatment consists of methylprednisolone at a dose of 2 mg/kg/d or equivalent that produces response rates of 63% to 95% for grade II, 17% to 39% for grade III, and 0% to 6% for grade IV aGVHD. In aggregate, approximately 40% to 50% of patients with acute GVHD experience a complete or partial response with primary therapy, whereas 20% to 60% require salvage treatments. The 1994 consensus conference on acute GVHD grading reported 100-day survival rates of 78% to 90% with grade I, 66% to 92% with grade II, 29% to 62% for grade III, and 23% to 25% for grade IV. The higher mortality rates were directly attributable to acute GVHD or to the subsequent immunosuppression from high-dose corticosteroids and other medications required for treatment of GVHD. Despite several studies seeking to improve first-line therapy for acute GVHD, standard care remains moderate-dose corticosteroids. Higher initial doses of corticosteroids, a more prolonged steroid tapering course, and addition of murine or equine anti-T-cell antibodies to standard GVHD therapy all failed to improve response rates. Acute GVHD therefore remains an unfavorable complication of transplantation that is difficult to manage. Various immunosuppressants including, Anti-thimocyte globulin (ATG), Denileukin Diftitox, Mycophenolate mofetil, Pentostatin, Infliximab, Rapamycin, Inolimomab and Daclizumab have been tried with variable success (table-1 in full protocol); there remains no consensus on the second-line treatment of aGVHD. Acute graft-versus-host-disease (aGVHD) is mediated by donor T-cells. The preventative and therapeutic strategies described above have therefore focused on quantitative reduction in T cells or reduction of their function through immune-modulation. The role of B-lymphocytes in the pathogenesis of GHVD is unclear. Recent reports of successful use of rituximab in cGVHD support the hypothesis that a coordinated B and T cell response is instrumental in cGVHD. The significance of B-cells in pathogenesis of aGVHD is unknown. Steroid Refractory Acute Graft-Versus-Host-Disease (SR-aGVHD) Initial treatment for aGVHD routinely consists of intensifying the dose of corticosteroids. This condition is called steroid-resistant (SR) aGVHD and requires secondary intervention. Rituximab is a human/murine chimeric monoclonal anti CD-20 antibody that is extensively used in patients with B-cell non-Hodgkin's lymphoma, or with autoimmune disease. The incidental observation of improvement in aGVHD following rituximab infusion for transplant-associated thrombotic thrombocytopenic purpura (TA-TTP) and subsequent complete resolution of multi-agent refractory aGVHD in two patients forms the basis of this proposed pilot study. Table-2 (in full protocol) describes the patients and their responses to rituximab at our own institution.

Conditions

• Graft vs Host Disease
• Alogenic Hematopoietic Transplant

Interventions

Type	Name	Description
DRUG	Rituximab	Rituximab 375 mg/m\^2 is given weekly X 4. For patients with a partial response, an additional 4 doses will be permitted as needed (after 4 weeks from the last dose). Diagnosis of grade II to IV aGVHD will be confirmed, whenever possible, by a biopsy taken from at least one of the following three sites: skin, gut, or liver.

Timeline

• Start date: 2007-06-01
• First posted: 2007-12-21
• Last updated: 2012-07-09

Locations

2 sites across 1 country: United States