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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Lymphoma; Leukemia; Small Intestine Cancer

Treatments: Drug: clofarabine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00416351

06-065

P30CA008748 (U.S. NIH Grant/Contract)

MSKCC-06065

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 29 patients

Sex: All

Ages: 2 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Clofarabine

Experimental group

Description:

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.

Treatment:

Drug: clofarabine