• Toxicity during treatment [ Designated as safety issue: Yes ]
• Maximum tolerated dose during treatment [ Designated as safety issue: Yes ]

• Toxicity during treatment
• Maximum tolerated dose during treatment

RATIONALE: Drugs used in chemotherapy, such as etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone, use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as alemtuzumab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of alemtuzumab when given together with combination chemotherapy in treating patients who have not previously received chemotherapy for T-cell or NK-Cell lymphoma.

OBJECTIVES:

Primary

• Determine the toxicity of alemtuzumab and etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) in patients with chemotherapy-naïve CD52-expressing aggressive T- or NK-cell lymphoma.
• Determine the maximum tolerated dose of alemtuzumab when administered with EPOCH chemotherapy in these patients.

Secondary

• Determine, preliminarily, the antitumor activity of this regimen in these patients.

OUTLINE: This is a pilot, dose-escalation study of alemtuzumab.

Patients receive alemtuzumab IV over 12 hours on day 1 and EPOCH chemotherapy comprising etoposide IV, doxorubicin IV, and vincristine IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 15 minutes on day 5; and oral prednisone twice daily on days 0-5. Patients also receive filgrastim subcutaneously on day 6. Treatment repeats every 21 days for 6-8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of alemtuzumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued to this study within 2.5 years.

• Biological: alemtuzumab
• Biological: filgrastim
• Drug: cyclophosphamide
• Drug: doxorubicin hydrochloride
• Drug: etoposide
• Drug: prednisone
• Drug: vincristine sulfate

DISEASE CHARACTERISTICS:

• Diagnosis of aggressive T- or NK-cell lymphoma, including, but not limited to any of the following:

  • Peripheral T-cell lymphoma not otherwise specified
  • Gamma-delta hepatosplenic T-cell lymphoma
  • Subcutaneous panniculitis-like T-cell lymphoma

• CD52-positive disease by pathology or flow cytometry

  • T- and NK-cell malignancy without accessible tissue for flow cytometry analysis allowed
• Chemotherapy-naïve disease
• No anaplastic large cell lymphoma (ALCL) except alk-negative ALCL
• No T-cell precursor disease

PATIENT CHARACTERISTICS:

Age

• 17 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,000/mm^3*
• Platelet count at least 75,000/mm^3* NOTE: *Unless due to organ involvement by tumor

Hepatic

• Bilirubin less than 2.0 mg/dL (unless due to Gilbert's syndrome)
• AST and ALT no greater than 3 times upper limit of normal (ULN) (6 times ULN for patients on hyperalimentation)

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No active symptomatic ischemic heart disease within the past year
• No myocardial infarction within the past year
• No congestive heart failure within the past year

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No other concurrent medical condition or infection that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed
• No other concurrent biologic therapy

Chemotherapy

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy

• Prior steroids allowed
• No other concurrent endocrine therapy

Radiotherapy

• No prior or concurrent radiotherapy

Surgery

• Not specified