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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/II Study of Clofarabine in Patients With Relapsed T-Cell and NK-Cell Lymphomas

Conditions
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Leukemia, Lymphoma, Small Intestine Cancer

Intervention / Treatment
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* Drug: clofarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clofarabine<br>Patients will receive intravenous clofarabine once daily for three consecutive days. Doses of clofarabine will start at 4 mg/m2/day and will be escalated to higher dose levels. | Drug: clofarabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | 2 years | 
| Response Rate for Participants With Non-Hodgkin's Lymphoma | Response rate as defined by complete remission, complete remission unconfirmed, partial remission, positron emission tomography (PET)-negative partial remission, stable disease, and progressive disease (Phase II) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Evaluated for Toxicity | Toxicity as defined by NCI Common Terminology Criteria for Adverse Events v 3.0 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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