Clofarabine in Treating Patients With T-Cell or Natural Killer-Cell Non-Hodgkin's Lymphoma That Has Relapsed or Not Responded to Previous Treatment

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of clofarabine in patients with relapsed or refractory T-cell or natural killer-cell lymphoma.
• Determine the toxicity of this drug in these patients.
• Determine, preliminarily, the efficacy of this drug, in terms of response rate, in these patients.

OUTLINE: This is a phase I, non-randomized, dose-escalation study followed by an open-label, phase II study.

• Phase I: Patients receive clofarabine IV over 1 hour once daily on days 1-3. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease or partial response (PR) or complete response (CR) may receive 2 additional courses of treatment. Patients with PR or CR after completing 4 courses of therapy may receive 2 additional courses.

Cohorts of 1-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive clofarabine as in phase I at the MTD determined in phase I.

After completion of study treatment, patients are followed every 3 months for 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed T-cell or natural killer (NK)-cell lymphoma, including any of the following subtypes:

• Blastic NK-cell lymphoma
• T/NK-cell lymphoma/leukemia
• Adult T-cell lymphoma/leukemia
• T-cell prolymphocytic leukemia
• T-lymphoblastic lymphoma
• Peripheral T-cell lymphoma, not otherwise specified
• Angioimmunoblastic T-cell lymphoma
• Anaplastic large cell lymphoma
• Transformed mycosis fungoides
• Subcutaneous panniculitis-like T-cell lymphoma
• Nasal T/NK-cell lymphoma
• Enteropathy-type T-cell lymphoma
• Hepatosplenic gamma/delta T-cell lymphoma
• Relapsed or refractory disease, meeting both of the following criteria:

• Must have been treated with prior cytotoxic chemotherapy and/or monoclonal antibody therapy
• No standard curative treatment exists

• Allogeneic bone marrow transplantation is not considered standard curative treatment
• Evaluable disease (Phase I)
• Measurable disease, defined as any nodal site or mass lesion ≥ 1.5 cm in longest transverse diameter on physical exam or CT scan OR a measurable extranodal site > 1 cm (Phase II)

• Patients with evaluable blood- or marrow-based disease are eligible

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,500/mm³ (Phase I)
• Absolute neutrophil count ≥ 500/mm³ (Phase II)
• Platelet count ≥ 100,000/mm³ (Phase I)
• Platelet count ≥ 50,000/mm³ (Phase II)
• Creatinine < 2.0 mg/dL*
• Bilirubin ≤ 2.0 times upper limit of normal (ULN)*
• AST and ALT ≤ 2.5 times ULN*
• No active infection requiring antibiotics
• No New York Heart Association class III or IV congestive heart failure
• No known HIV positivity
• No other active malignancy requiring therapy
• No other serious or life-threatening condition deemed unacceptable by the principal investigator
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception NOTE: *Unless due to lymphoma and patients are entering to the phase II portion of the study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 3 weeks since prior therapy, including any of the following:

• Interferon
• Antibody therapy
• Retinoids
• Other non-chemotherapeutic treatment
• Concurrent stable-dose corticosteroids allowed
• No colony-stimulating factor therapy during the first course of study therapy