Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

FR901228 in Treating Patients With T-Cell Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI NCI-01-C-0049 NCI-1312, NCT00020436, 1312

Special Category: NCI Web site featured trial

Objectives

Primary

1. 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).
2. Determine the duration of response in patients with CTCL treated with this drug.

Secondary

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

Entry Criteria

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)]

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

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/mm³*
• Platelet count at least 100,000/mm³*

 [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

Expected Enrollment

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

Outcomes

Overall response rate
Complete response rate
Duration of response

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Richard Piekarz, MD, PhD, Protocol chair		Ph: 301-402-3524 Email: rpiekarz@nih.gov

Related Information

Featured trial article

Registry Information
Official Title		Phase II Trial Of Depsipeptide In Patients With Cutaneous T-Cell Lymphoma And Relapsed Peripheral T-Cell Lymphoma
Trial Start Date		2000-12-28
Trial Completion Date		2001-04-14 (estimated)
Registered in ClinicalTrials.gov		NCT00020436
Date Submitted to PDQ		2001-01-02
Information Last Verified		2008-04-06