clofarabine in treating patients with t-cell or natural killer-cell non-hodgkin's lymphoma that has relapsed or not responded to previous treatment

Conditions: Leukemia; Lymphoma; Small Intestine Cancer

Summary: 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

Keywords: anaplastic large cell lymphoma angioimmunoblastic t-cell lymphoma recurrent adult lymphoblastic lymphoma recurrent adult t-cell leukemia/lymphoma recurrent mycosis fungoides/sezary syndrome adult nasal type extranodal nk/t-cell lymphoma prolymphocytic leukemia childhood nasal type extranodal nk/t-cell lymphoma recurrent childhood lymphoblastic lymphoma recurrent cutaneous t-cell non-hodgkin lymphoma small intestine lymphoma