A Phase II Prospective Non-Randomized Clinical Trial of Dose-Adjusted Schedule of Vorinostat in Patients With Primary Cutaneous T-Cell Lymphoma Who Did Not Receive Prior Systemic Therapy or Have Been Treated With Single Agent Targretin
Overview
- Phase
- Phase 2
- Intervention
- vorinostat
- Conditions
- Cutaneous T-cell Lymphoma Stage I
- Sponsor
- University of Washington
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Objective Response
- Status
- Terminated
- Last Updated
- 7 years ago
Overview
Brief Summary
This phase II trial studies the side effects and how well vorinostat works in treating patients with primary cutaneous T-cell lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth
Detailed Description
PRIMARY OBJECTIVES: I. To determine the objective response rate to treatment with dose-adjusted Vorinostat schedule in subjects with cutaneous T-cell lymphoma (CTCL) who did not receive prior systematic therapy or have been treated with single agent targretin (bexarotene). SECONDARY OBJECTIVES: I. To determine the safety and tolerability of dose-adjusted Vorinostat schedule when administered to patients with primary cutaneous T-cell lymphoma who did not receive prior systematic therapy or have been treated with single agent targretin. II. To determine the time to objective response in subjects with CTCL treated with dose-adjusted schedule of Vorinostat as primary therapy. III To determine the duration of objective response in subjects with CTCL. IV. To determine the time to loss of objective response. V. To determine the objective response rate of extracutaneous manifestations of CTCL (lymph node enlargement, Sezary cells in peripheral blood). VI. To compare the efficacy, toxicity and tolerability of dose-adjusted schedule to currently recommended flat dose of Vorinostat in subjects with CTCL. OUTLINE: Patients are assigned to 1 of 2 treatment arms according to age (\< 65 vs \>= 65 years old). COHORT I (\>= 65 years old): Patients receive 200 mg vorinostat orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. COHORT II (\< 65 years old): Patients receive 400 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.
Investigators
Andrei Shustov
Principal Investigator
University of Washington
Eligibility Criteria
Inclusion Criteria
- •Males or non-pregnant females
- •Histologically confirmed diagnosis of CTCL, including mycosis fungoides and/or Sezary syndrome
- •Documentation of diagnosis by histologic examination should be available
- •Subjects with CTCL stages IB, IIA, IIB, III, or IVA who have not received any prior systemic therapies
- •Anticipated life expectancy greater than 6 months
- •Performance status 0, 1, or 2 by Eastern Cooperative Oncology Group (ECOG) criteria
- •Written informed consent to participate in the study
- •Absolute neutrophil count (ANC) \>= 1,000/mcL
- •Platelets \>= 75,000/mcL
- •Hemoglobin \>= 9 g/dL
Exclusion Criteria
- •Proven or suspected extracutaneous visceral CTCL involvement (M1) (CTCL stage IVB)
- •Presence of lymphadenopathy is permitted
- •ECOG performance status \> 2
- •Concomitant use of any anti-cancer therapy or immune modifier
- •Concomitant use of any investigational agent or device
- •Concomitant therapy with any other anti-CTCL therapy, or radiation therapy (topical corticosteroids or low dose oral corticosteroids \[=\< 10 mg/day prednisone or equivalent\] will not be excluded, but if used, the dose and schedule must be stable during the two weeks immediately prior to study entry)
- •Use of any previous systemic therapy (except single agent targretin), total skin electron beam (TSEB) therapy or extracorporeal photopheresis
- •Evidence of clinically significant (uncontrolled) hypo- or hyperthyroidism
- •Poorly controlled diabetes mellitus as evidenced by hemoglobin (Hgb)A1c \> 6.5 mg/dl
- •Recent (in the past 6 months) medically significant cardiac event (i.e. myocardial infarction, cardiac surgery)
Arms & Interventions
Cohort I (>=65 years old)
200 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses. Dose escalation by 100mg per day increments to maximum dose of 500mg per day in the absence of dose limiting toxicity.
Intervention: vorinostat
Cohort I (>=65 years old)
200 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses. Dose escalation by 100mg per day increments to maximum dose of 500mg per day in the absence of dose limiting toxicity.
Intervention: flow cytometry
Cohort I (>=65 years old)
200 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses. Dose escalation by 100mg per day increments to maximum dose of 500mg per day in the absence of dose limiting toxicity.
Intervention: laboratory biomarker analysis
Cohort II (<65 years old)
400 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses. Dose escalation by 100mg per day increments to maximum dose of 500mg per day in the absence of dose limiting toxicity.
Intervention: vorinostat
Cohort II (<65 years old)
400 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses. Dose escalation by 100mg per day increments to maximum dose of 500mg per day in the absence of dose limiting toxicity.
Intervention: flow cytometry
Cohort II (<65 years old)
400 mg vorinostat PO QD on days 1-28. Treatment repeats every 28 days for 6 courses. Dose escalation by 100mg per day increments to maximum dose of 500mg per day in the absence of dose limiting toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Objective Response
Time Frame: After at least 14 days. With Confirmation after additional 28 days.
Defined as either no evidence of clinical disease or marked improvement (\>= 50%) decrease in the modified Severity-Weighted Assessment Tool (mSWAT) skin assessment score compared to baseline.
Secondary Outcomes
- Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood);(Up to 30 days post-treatment)
- Occurrences of Dose Adjustment as Measured by Safety/Toxicity(Up to 30 days post-treatment)
- Number of Participants With Overall Response as Measured by Sezary Cell Count(Baseline to 30 days post-treatment)
- Changes in the Physicians Serial Assessment of Erythroderma Score(Baseline to 30 days post-treatment)