Methotrexate and Glucocorticoids in Treating Patients With Newly Diagnosed Acute Graft-Versus-Host Disease After Donor Stem Cell Transplant
RATIONALE: Methotrexate and glucocorticoid therapy, such as prednisone or methylprednisolone, may be an effective treatment for acute graft-versus-host disease caused by a donor stem cell transplant.
PURPOSE: This phase II trial is studying how well giving methotrexate together with glucocorticoids works in treating patients with newly diagnosed acute graft-versus-host disease after donor stem cell transplant.
|Study Design:||Primary Purpose: Supportive Care|
|Official Title:||A Phase II Study to Evaluate Efficacy and Tolerability of Methotrexate in Combination With Glucocorticoids for the Treatment of Newly Diagnosed Acute Graft-Versus-Host Disease After Nonmyeloablative Hematopoietic Cell Transplantation|
- Proportion of patients treated with a methylprednisolone-equivalent glucocorticoid dose ≤ 0.75 mg/kg on day 28 after initiation of systemic glucocorticoid therapy for acute graft-versus-host disease (GVHD) [ Designated as safety issue: No ]
- Proportion of patients in whom methotrexate (MTX) had to be discontinued because of toxicity [ Designated as safety issue: Yes ]
- Incidence of severe acute GVHD (grades III or IV) [ Designated as safety issue: Yes ]
- Incidence of extensive chronic GVHD [ Designated as safety issue: Yes ]
- Incidence of secondary systemic immunosuppressive therapy [ Designated as safety issue: Yes ]
- Cumulative corticosteroid use over 1 year [ Designated as safety issue: No ]
- Nonrelapsing mortality at 1 year [ Designated as safety issue: Yes ]
- Incidence of invasive mold infections [ Designated as safety issue: Yes ]
- Incidence of recurrent/progressive malignancy [ Designated as safety issue: Yes ]
- Cumulative dose of methylprednisolone-equivalent treatment during the first 8 weeks after enrollment in patients who survive to day 56 [ Designated as safety issue: No ]
|Study Start Date:||May 2006|
|Primary Completion Date:||August 2007 (Final data collection date for primary outcome measure)|
- Determine, within the limits of a phase II study, whether low-dose methotrexate can accelerate withdrawal of glucocorticoids and decrease nonrelapsing mortality in patients with newly diagnosed acute graft-versus-host disease (GVHD) who have undergone nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT).
- Determine the tolerability of low-dose methotrexate and glucocorticoids in treating newly diagnosed acute GVHD in these patients.
OUTLINE: This is a cohort study. Patients receive concurrent low-dose methotrexate and a glucocorticoid for treatment of acute graft-versus-host disease (GVHD).
Patients receive the first dose of methotrexate IV ≥ 12 hours before initiation of glucocorticoid treatment (if glucocorticoid treatment has not been initiated) and the second dose 72 hours after dose 1. Patients then receive subsequent doses of methotrexate IV or orally once weekly for up to 1 year* until resolution of GVHD in the absence of recurrent malignancy, refractory or chronic GVHD, administration of secondary treatment for GVHD, or unacceptable toxicity.
NOTE: *Treatment with low-dose MTX may continue beyond 1 year at the discretion of the managing physician.
Patients receive glucocorticoid therapy comprising prednisone or methylprednisolone IV twice daily until objective evidence of improvement in GVHD manifestation. Patients with resolved or significantly improved GVHD receive treatment for 10 days followed by an accelerated taper for a total of 72 days of treatment in case of no flare up of GVHD during the glucocorticoid taper. Patients with exacerbation or recurrence of GVHD during the accelerated taper are treated for ≥ 1 week before resuming a less rapid taper. Patients who develop GVHD progression or primary refractory GVHD may receive secondary systemic therapy at the discretion of the managing physician.
After completion of study treatment, patients are followed at 1 year and then annually thereafter.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00357084
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Marco B. Mielcarek, MD||Fred Hutchinson Cancer Research Center|