A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-Host Disease
- Determine whether the administration of low-dose alemtuzumab at the onset of acute
graft-versus-host disease can accelerate withdrawal of glucocorticoids and decrease
nonrelapsing mortality in patients who have undergone myeloablative allogeneic stem
OUTLINE: This is an open-label, nonrandomized study.
Within 72 hours of beginning glucocorticoid therapy, patients receive alemtuzumab IV over at
least 2 hours on days 1 and 2. If graft-versus-host disease (GVHD) responds well during days
1-14 but returns between days 28 and 56, patients are eligible to receive 2 additional doses
Patients receive glucocorticoid therapy comprising methylprednisolone IV or oral prednisone
daily until objective evidence of improvement in manifestations of GVHD. Patients with
resolved or significantly improved GVHD receive treatment until day 10 followed by an
accelerated taper until day 72 if no flare up of GVHD occurs during the glucocorticoid
taper. Patients with recurrent or progressive GVHD during the accelerated taper are treated
for 5-7 days before resuming a less rapid taper. Patients with no improvement may receive
secondary therapy with alternative immunosuppressive medications at the discretion of the
managing physician. Treatment continues in the absence of progressive GVHD of at least 3
days duration during days 2-10; persisting GVHD without improvement between days 10-14;
recurrent or progressive GVHD after day 10 that does not respond within 3 days to topical
immunosuppressive therapy; and/or an increase in the systemic glucocorticoid dose by two
taper steps; or unacceptable toxicity.
Patients undergo blood collection at baseline and then periodically during study treatment
for pharmacokinetics and quantification of viral loads for human herpes virus 6, adenovirus,
Epstein-Barr virus, and cytomegalovirus. Samples are also examined by flow cytometry for B-
and T-cell quantification at baseline, periodically during study treatment, and at 1 year
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Supportive Care
Proportion of patients with methylprednisolone (MP)-equivalent glucocorticoid doses ≤ 0.75 mg/kg on day 28 after starting therapy for graft-versus-host disease (GVHD)
Paul Carpenter, MD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|