Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Suberoylanilide Hydroxamic Acid in Treating Patients With Progressive, Persistent, or Recurrent Cutaneous T-Cell Lymphoma

Basic Trial Information

Objectives

Primary

1. Determine the response rate in patients with skin disease associated with progressive, persistent, or recurrent stage IB-IV cutaneous T-cell lymphoma treated with suberoylanilide hydroxamic acid.

Secondary

1. Determine the time to objective response, response duration, and time to progression in patients treated with this drug.
2. Determine the relief of pruritus in patients treated with this drug.
3. Determine the safety and tolerability of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed cutaneous T-cell lymphoma, including Sézary syndrome (SS), within the past year
  • Stage IB-IV disease

• Progressive, persistent*, or recurrent disease during or after ≥ 2 prior systemic therapies (parenteral or oral), 1 of which contained bexarotene**
  • The following are considered systemic therapy:
    • An antineoplastic agent in combination with photopheresis
    • Standard combination chemotherapy (e.g., CHOP, CVP, or CAP) in combination with bexarotene
    • Standard combination chemotherapy (e.g., CHOP, CVP, or CAP) in combination with a biologic agent (e.g., interferon or denileukin diftitox)
    • A biologic agent in combination with bexarotene
    • A cytotoxic agent (e.g., methotrexate or gemcitabine) in combination with bexarotene
    • A cytotoxic agent in combination with a biologic agent

   [Note: *Persistent disease defined as < 50% improvement of disease during ≥ 3 months of prior therapy unless patient is intolerant to therapy due to toxic effects]

   [Note: **Unless patient is intolerant of (discontinued bexarotene due to toxic effects) or not a candidate (due to presence of risk factors for pancreatitis) for bexarotene]

• Has tumor-related symptoms (e.g., pruritus)

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• No concurrent biologic therapy
• No concurrent prophylactic hematologic growth factors

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (including topical chemotherapy and photopheresis) unless there is rapid disease progression
• No concurrent chemotherapy, including photopheresis

Endocrine therapy

• No concurrent systemic steroids except for patients with SS
  • Patients with SS who have been on systemic steroids for the past 3 months AND who have been on a stable daily dose of steroids (equivalent to ≤ 10 mg of prednisone) within the past 4 weeks are eligible
• No concurrent topical steroids
  • Patients who have been using topical steroids for the past 3 months or longer are eligible provided the dosage is ≤ 0.1% triamcinolone acetonide cream (Aristocort A® 0.1% cream or similar strength steroid cream) for the past 4 weeks

Radiotherapy

• At least 3 weeks since prior radiotherapy unless there is rapid disease progression
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior major surgery unless there is rapid disease progression

Other

• Recovered from all prior therapy
• At least 3 weeks since prior psoralen and ultraviolet light (PUVA)*
• At least 3 weeks since prior investigational anticancer therapy*
• No prior histone deacetylase inhibitors (e.g., FR901228, MS-275, or LAQ-824)
• No concurrent topical or oral retinoids
• No concurrent PUVA
• No concurrent vitamin A
• No other concurrent vitamins except for a single daily multivitamin
• No other concurrent investigational anticancer therapy
• No other concurrent investigational drugs

 [Note: *Unless there is rapid disease progression]

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of tumor involvement to the liver)
• No active hepatitis B or C infection

Renal

• Creatinine ≤ 2 mg/dL

  OR

• Creatinine clearance > 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Immunologic

• No known allergy to any component of the study drug
• No ongoing or active infection
• No known HIV infection
• No acute infection requiring IV antibiotics or antifungal agents

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to swallow capsules
• No psychiatric illness or social situation that would preclude study compliance
• No other cancer within the past 5 years except basal cell carcinoma
• No other uncontrolled illness
• No circumstance that would preclude study participation

Expected Enrollment

Approximately 70 patients (at least 50 with stage IIB-IV disease) will be accrued for this study within 1 year.

Outline

This is an open-label, nonrandomized, multicenter study.

Patients receive oral suberoylanilide hydroxamic acid once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed within 4 weeks and then annually thereafter.

Olsen EA, Kim YH, Kuzel TM, et al.: Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25 (21): 3109-15, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Lauren Pinter-Brown, MD, Protocol chair		Ph: 818-364-3205 Email: lpb@ucla.edu

Registry Information
Official Title		Phase IIB Multicenter Clinical Trial of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Advanced Cutaneous T-Cell Lymphoma
Registered in ClinicalTrials.gov		NCT00091559
Date Submitted to PDQ		2005-05-11
Information Last Verified		2007-07-30
NCI Grant/Contract Number		P30-CA16042