• Overall response rate [ Designated as safety issue: No ]
  
• Complete response rate [ Designated as safety issue: No ]
  
• Duration of response [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the overall and complete response rates in patients with cutaneous T-cell lymphoma (CTCL), relapsed peripheral T-cell lymphoma, or other mature T-cell lymphoma treated with FR901228 (depsipeptide).
• Determine the duration of response in patients with CTCL treated with this drug.

Secondary

• Determine the tolerability of this drug with extended courses of therapy in these patients.
• Determine the molecular effects of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 197 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

  • Histologically confirmed cutaneous T-cell lymphoma (CTCL) (mycosis fungoides or Sezary syndrome)

    • Stage IB or IIA

      • Refractory to, intolerant of, or at a 6-month or longer response plateau on at least 2 of the following prior therapies:

        • Phototherapy (psoralen ultraviolet light, ultraviolet B light, or EBT), photophoresis, interferon, systemic cytotoxic chemotherapy, topical nitrogen mustard, or topical carmustine
        • One prior therapy must have been phototherapy, topical nitrogen mustard, or topical carmustine
        • Topical steroids, systemic retinoids, and biologicals do not qualify

    • Stage IIB-IVB

      • CTCL previously treated with vorinostat
  • Peripheral T-cell lymphoma, unspecified or anaplastic large cell lymphoma, T and null cell, primary cutaneous type*

  • Other mature T-cell lymphoma* not listed above including, but not limited to:

    • Enteropathy-type T-cell lymphoma
    • Hepatosplenic T-cell lymphoma
    • Subcutaneous panniculitis-like T-cell lymphoma
    • Angioimmunoblastic T-cell lymphoma
• No primitive T-cell neoplasm or T-cell leukemia
• Measurable disease by radiographic imaging, assessment of skin lesions, or quantitating Sezary cell count
• No B-cell lymphoma
• No known CNS lymphoma NOTE: *Disease progression after prior standard therapy (> 2 prior systemic cytotoxic chemotherapy regimens)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3*
• Platelet count at least 100,000/mm^3* NOTE: *Unless decreased levels are due to bone marrow involvement by lymphoma

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)*
• AST no greater than 3 times ULN* NOTE: *Unless elevated levels are due to liver involvement by lymphoma

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No myocardial infarction within the past 12 months
• No active coronary artery disease (e.g., angina, defined by Canadian Class II-IV)
• No congenital long QT syndrome
• QTc ≤ 480 msec
• No cardiac ischemia (ST depression ≥ 2 mm) by ECG
• No Mobitz II second-degree heart block without a pacemaker

• Cardiology consultation and/or Holter monitoring required for any 1 of the following:

  • Coronary artery disease (no active myocardial ischemia)
  • History of arrhythmia
  • First-degree or Mobitz I second-degree heart block
  • Bradyarrhythmia
  • Sick sinus syndrome
• No New York Heart Association class II-IV congestive heart failure
• Ejection fraction ≥ 50% by echocardiogram or cardiac MRI OR ≥ 45% by MUGA scan
• No history of sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, or cardiac arrest unless supported by an automatic implantable cardioverter defibrillator (AICD)
• No dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or other causes
• No uncontrolled hypertension (i.e., blood pressure ≥ 160/95 mmHg)

• No cardiac arrhythmia requiring anti-arrhythmic medication

  • Beta blockers or calcium channel blockers allowed
  • Must discontinue digitalis therapy
• Other cardiac disease may be excluded at the discretion of the protocol investigator and cardiologist

Other:

• HIV negative
• No other serious or concurrent illness
• No uncontrolled infection
• No uncontrolled medical illness
• No prior or concurrent malignancy not curatively treated
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• More than 2 weeks since prior biologic or immunotherapy

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• No more than 2 prior systemic cytotoxic chemotherapy regimens (for patients with cutaneous T-cell lymphoma)

  • Radiolabeled monoclonal antibody therapy is counted toward the prior regimens
  • No limit on prior regimens for patients with other mature T-cell lymphoma
• No other concurrent chemotherapy, including topical agents

Endocrine therapy:

• See Disease Characteristics
• Concurrent corticosteroids for symptom management allowed provided dose is stable for more than 1 month

Radiotherapy:

• Prior localized external-beam radiotherapy allowed
• Concurrent localized external-beam radiotherapy for palliation of metastatic disease allowed if evidence of response to study drug
• No concurrent localized external-beam radiotherapy for disease progression

Surgery:

• At least 3 weeks since prior major surgery
• Concurrent surgery for palliation of metastatic disease allowed if evidence of response to study drug
• No concurrent surgery for disease progression

Other:

• Prior complementary and alternative medications allowed
• No concurrent complementary and alternative medications

• No concurrent medications that prolong the QTc interval

  • At least 5 half-lives after administration of medications that prolong the QTc interval