Active clinical trials for "Graft vs Host Disease"

The main objective of the study is to improve the response rate (complete and partial remission) at 12 months after diagnosis of chronic Chronic Graft Versus Host Disease (GVHD) and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.

The purpose of this study is to extend the use of Tacrolimus and Sirolimus to determine how effective it is in preventing graft versus host disease (GVHD)in patients that have received non-myeloablative peripheral blood stem cell transplantation.

The addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, enable a more rapid and effective steroid taper.

RATIONALE: Donor mesenchymal stem cell infusion may be an effective treatment for acute or chronic graft-versus-host disease caused by a donor stem cell transplant. PURPOSE: This phase I trial is studying the side effects and best dose of donor mesenchymal stem cells in treating patients with acute or chronic graft-versus-host disease after undergoing a donor stem cell transplant.

Graft-vs.-Host Disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT) commonly affecting the skin, liver, gastrointestinal tract, and eye. The most common clinical manifestations of ocular GVHD generally result from involvement of the lacrimal gland and the conjunctiva. Lacrimal gland involvement can lead to aqueous tear deficiency resulting in severe keratoconjunctivitis sicca (KCS) which can significantly increase the morbidity of patients with chronic GVHD. Systemic immunosuppressants such as cyclosporine (CsA) can be effective for treating ocular GVHD including lacrimal gland dysfunction. However, systemic immunosuppression is not generally prescribed for patients whose sole manifestation of GVHD is ocular complications as it may negate the overall graft-vs.-tumor effect and decrease patient survival. Topical CsA and corticosteroids are generally not effective for treating aqueous tear deficiency possible due to epithelial barriers preventing penetration of the drugs to the lacrimal gland. A sustained-release subconjunctival CsA implant was developed to bypass these epithelial barriers and significantly increase the CsA concentrations in the lacrimal gland to treat aqueous tear deficiency related to GVHD. The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in patients with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction. Patients with active systemic GVHD with aqueous tear deficiency associated with lacrimal gland dysfunction following allogeneic hematopoietic SCT who are nine years of age or older are eligible for inclusion in this pilot study. The study will involve surgical placement of the CsA implant into the subconjunctival space adjacent to the lacrimal gland of one eye in each participant. Participants older than 12 years of age will be randomized to receive one of two implant release rates. All participants under the age of 12 will receive the smaller, lower dose implant. However, all participants under age 12 will not be randomized and will only be eligible to receive the smaller, lower dose implant. The implant will remain in place for up to two years and then be removed. IF the participant has clinical success, they will be given the option of allowing the implant to remain in place for an additional year. Clinical success is achieved if the participant meets any of the following measures in either eye assessed at the 1-year visit: Interval change from baseline characteristics Decrease in corneal staining by greater than or equal to 2 Decrease in temporal or nasal conjunctival staining grades by greater than or equal to 2 Decrease in total staining grade by greater than or equal to 2 Decrease in OSDI calculated score by greater than or equal to 20% Increase in Schirmer tear test measurement by greater than or equal to 3 mm Meets mild-moderate KCS characteristics at 1 year Corneal staining grade less than or equal to 3 Nasal or temporal conjunctival staining grades less than or equal to 3 OSDI calculated score less than or equal to 15 Schirmer tear test measurement greater than or equal to 5 mm For participants with implant duration of one year, safety evaluations will be conducted at baseline (pre-implantation) and monthly post-implantation for 13 months. Additional safety assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant placement and removal procedures. Safety and efficacy evaluations will be conducted at baseline, at 1, 3, 6, 9, and 12 months post-implantation, and at 3 months following implant removal (15 months post-implantation). For participants with clinical success and who choose the implant to remain for another year, visits will be held as described above then conducted at 2-month intervals starting at month 14. Safety evaluations will be conducted every 2 months until the end of the second year. Additional safety assessments will be done at 1 day, and at 1 and 2 weeks post-operatively for implant removal procedures. Safety and efficacy evaluations will be conducted at 16, 20, and 24 months post-implantation, and at 3 months following implant removal (27 months post-implantation).

To establish the safety and efficacy of two dose levels of ex-vivo cultured adult human mesenchymal stem cells (hMSCs) (Prochymal®) in participants experiencing acute GVHD, Grades II-IV, post hematopoietic stem cells (HSC) transplant.

The study is a randomized Phase II, four arm treatment trial. The primary purpose of the study is to define new agents with promising activity against acute graft-versus-host disease (GVHD) suitable for testing against corticosteroids alone in a subsequent Phase III trial.

Renal function at 12 months assessed by calculated creatinine clearance.

The purpose of this Phase I/II, open-label, dose-escalation study is to evaluate an investigational monoclonal antibody administered as a first-line therapy to patients with acute, Grade II, III, or IV graft-versus-host disease (GVHD). Patients will be eligible for enrollment within 24 hours of beginning standard steroid treatment. The research is being conducted at up to 10 clinical research sites in the US.

The purpose of this study is to compare the effects of IL2 receptor antibody (also known as Daclizumab or Zenapax) and corticosteroids alone for control of GVHD. Treatment with corticosteroids is standard care for GVHD. This research is being done because the investigators do not know whether addition of this new medication to standard corticosteroid therapy improves response rates. Since Zenapax binds to a type of cell which is thought to cause GVHD and possibly inactivates them, investigators have reason to believe that addition of Zenapax night result in better control of GVHD This study will determine whether the addition of another medication, Zenapax, will be more effective than steroids alone in suppressing GVHD and improving symptoms of GVHD. Daclizumab (Zenapax) is approved by the Food and Drug Administration (FDA) for use in patient with kidney transplant to help prevent graft rejection. This medication has been used in bone marrow transplant patients to treat GVHD.