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

RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine and to see how well it works in treating patients with T-cell or natural killer-cell 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.

Eligibility Criteria:
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