Alemtuzumab and Glucocorticoids in Treating Newly Diagnosed Acute Graft-Versus-Host Disease in Patients Who Have Undergone a Donor Stem Cell Transplant
RATIONALE: Alemtuzumab and glucocorticoids, 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 alemtuzumab together with glucocorticoids works in treating newly diagnosed acute graft-versus-host disease in patients who have undergone donor stem cell transplant.
|Breast Cancer Chronic Myeloproliferative Disorders Gestational Trophoblastic Tumor Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Neuroblastoma Ovarian Cancer Testicular Germ Cell Tumor||Biological: alemtuzumab Drug: methylprednisolone Drug: prednisone Other: flow cytometry Other: immunologic technique Other: pharmacological study||Phase 2|
|Study Design:||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Supportive Care
|Official Title:||A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-Host Disease|
- 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)
- Total cumulative dose of MP-equivalent treatment during the first 8 weeks after study entry
- Proportion of patients with complete response, measured weekly through day 56
- Incidence of secondary systemic therapy for acute GVHD
- Cumulative acute GVHD activity index score at day 56
- Incidence of chronic GVHD at 1 year
- Nonrelapsing mortality at 1 year
- Survival at 1 year
- Cumulative incidence of opportunistic infections at 1 year
- Cumulative incidence of recurrent or progressive malignancy at 1 year
- Peripheral blood CD4, CD8, CD19, and CD16/56 counts at baseline and then periodically for 1 year
|Study Start Date:||July 2006|
|Primary Completion Date:||November 2006 (Final data collection date for primary outcome measure)|
- 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 cell transplantation.
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 of alemtuzumab.
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 transplantation.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00410657
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Principal Investigator:||Paul Carpenter, MD||Fred Hutchinson Cancer Research Center|