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
- 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
NOTE: *Treatment with low-dose MTX may continue beyond 1 year at the discretion of the
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
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Primary Purpose: Supportive Care
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)
Marco B. Mielcarek, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|