Alemtuzumab Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Lymphocytic Leukemia

OBJECTIVES:

• Determine the ability of in vivo purging with alemtuzumab (monoclonal antibody CD52; Campath-1H) to produce a stem cell graft without detectable leukemia cells in patients with chronic lymphocytic leukemia.
• Determine the ability to successfully mobilize stem cells after in vivo purging with monoclonal antibody CD52 in these patients.
• Determine the toxicity of this treatment regimen in these patients.
• Determine the response to this treatment regimen in these patients at 6 months after peripheral blood stem cell transplantation.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising alemtuzumab (monoclonal antibody CD52; Campath-1H) IV over 2 hours three times a week for 4 weeks.

Beginning no more than 2 weeks after induction therapy, patients receive mobilization chemotherapy comprising cyclophosphamide IV over 1-2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) starting on day 2 and continuing until the last day of apheresis. Patients undergo peripheral blood stem cell apheresis on days 10-14.

Beginning 2-4 weeks after apheresis, patients receive a preparative regimen comprising cyclophosphamide IV over 2 hours on days -5 and -4 and fractionated total body irradiation twice a day over 6-10 hours on days -3 to -1. Patients undergo peripheral blood stem cell transplantation on day 0. Patients receive G-CSF SC beginning on day 1 and continuing until blood counts recover.

Patients are followed at 60 days, 1 year, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) that meets the following criteria at any point prior to study entry:

• Peripheral blood absolute blood count greater than 5,000/mm^3
• Lymphocytosis must comprise small to moderate size lymphocytes with no more than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically
• Phenotypically characterized B-cell CLL
• Splenomegaly, hepatomegaly, or lymphadenopathy not required for CLL diagnosis
• Must have bone marrow biopsy within 4 weeks of study entry showing cellularity of at least 25% of intratrabecular space and lymphocytes accounting for no more than 30% of nucleated cells

PATIENT CHARACTERISTICS:

Age:

• 18 to 65

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3
• Hemoglobin at least 11 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 mg/dL (unless secondary to tumor)
• AST or ALT less than 3 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C RNA negative

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• Left ventricular ejection fraction at least 45% by echocardiogram or MUGA

Pulmonary:

• DLCO, FEV_1, and FVC greater than 50% of predicted

Other:

• No active infection requiring oral or IV antibiotics
• No other prior malignancy within the past two years except basal cell skin cancer or carcinoma in situ of the cervix
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior monoclonal antibody CD52 allowed if at least partial remission was achieved with last treatment

Chemotherapy:

• No more than 2 prior chemotherapy regimens
• At least 3 weeks since prior chemotherapy
• No more than 8 courses of prior fludarabine therapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified