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

May 12, 2010 updated by: Fred Hutchinson Cancer Center

A Phase II Study to Evaluate Low-Dose Alemtuzumab as a Glucocorticoid-Sparing Agent for Initial Systemic Treatment of Acute Graft-Versus-Host Disease

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Anticipated)

53

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Washington
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Non-Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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)

Secondary Outcome Measures

Outcome Measure
Survival at 1 year
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Paul Carpenter, MD, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

December 11, 2006

First Submitted That Met QC Criteria

December 11, 2006

First Posted (Estimate)

December 13, 2006

Study Record Updates

Last Update Posted (Estimate)

May 14, 2010

Last Update Submitted That Met QC Criteria

May 12, 2010

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2096.00
  • FHCRC-2096.00
  • CDR0000523371 (Registry Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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