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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00410657
• Other study ID #: 2096.00
• Secondary ID: FHCRC-2096.00CDR
• Status: Completed
• Phase: Phase 2
• First received: December 11, 2006
• Last updated: May 12, 2010
• Start date: July 2006

Study information

• Verified date: May 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Chronic Myeloproliferative Disorders
• Gestational Trophoblastic Disease
• Gestational Trophoblastic Tumor
• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Germ Cell and Embryonal
• Neoplasms, Plasma Cell
• Neuroblastoma
• Ovarian Cancer
• Plasmacytoma
• Preleukemia
• Testicular Germ Cell Tumor
• Testicular Neoplasms
• Trophoblastic Neoplasms

Intervention

Biological:
• alemtuzumab

Drug:
• methylprednisolone

• prednisone

Other:
• flow cytometry

• immunologic technique

• pharmacological study

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Total cumulative dose of MP-equivalent treatment during the first 8 weeks after study entry
Secondary	Proportion of patients with complete response, measured weekly through day 56
Secondary	Incidence of secondary systemic therapy for acute GVHD
Secondary	Cumulative acute GVHD activity index score at day 56
Secondary	Incidence of chronic GVHD at 1 year
Secondary	Nonrelapsing mortality at 1 year
Secondary	Survival at 1 year
Secondary	Cumulative incidence of opportunistic infections at 1 year
Secondary	Cumulative incidence of recurrent or progressive malignancy at 1 year
Secondary	Peripheral blood CD4, CD8, CD19, and CD16/56 counts at baseline and then periodically for 1 year