Alemtuzumab and Glucocorticoids in Treating Newly Diagnosed Acute Graft-Versus-Host Disease in Patients Who Have Undergone a Donor Stem Cell Transplant

NCT ID: NCT00410657

Last Updated: 2010-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

• 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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

methylprednisolone

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

flow cytometry

Intervention Type: OTHER

immunologic technique

Intervention Type: OTHER

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed acute graft-versus-host disease (GVHD)

• Grade IIB-IV disease
• Requires glucocorticoids for treatment of GVHD, as indicated by 1 of the following:

• Initial treatment with prednisone or methylprednisolone at 2 mg/kg is indicated (in the judgement of the attending physician) by any of the following:

• Severity of GVHD requires hospitalization
• GVHD manifestations include symptoms other than anorexia, nausea, and vomiting
• GVHD begins within 2-3 weeks after hematopoietic stem cell transplantation (HSCT)
• GVHD manifestations progress rapidly from 1 day to the next before treatment
• Initial treatment with prednisone or methylprednisolone at 1 mg/kg did not produce adequate clinical improvement within the first 4 days (in the judgement of the attending physician)
• Has undergone allogeneic HSCT with myeloablative conditioning

• No nonmyeloablative conditioning or autologous HSCT
• No primary treatment of acute GVHD with methylprednisolone at any of the following doses:

• More than 2 mg/kg/day at any time
• 2 mg/kg/day for > 72 hours
• 1 mg/kg/day for > 96 hours
• No presence of distinctive or diagnostic manifestations of chronic GVHD
• No relapsed, refractory, or secondary malignancy

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 20-100% OR Lanksy PS 20-100%
• Life expectancy ≥ 1 month
• Absolute neutrophil count ≥ 500/mm^3
• Negative pregnancy test
• No Mini Mental State Exam score < 24/30 or confusion (for patients > 12 years of age)
• No history of type I hypersensitivity reaction to alemtuzumab or any of its components
• No increasing levels of viremia by serial quantitative viral plasma polymerase chain reaction assays
• No invasive viral or fungal disease that does not respond to appropriate antiviral or antifungal medications

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No systemic immunosuppression tapered or stopped for treatment of leukemic relapse or minimal residual disease

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Paul Carpenter, MD

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

Locations

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

FHCRC-2096.00

Identifier Type: -

Identifier Source: secondary_id

CDR0000523371

Identifier Type: REGISTRY

Identifier Source: secondary_id

2096.00

Identifier Type: -

Identifier Source: org_study_id