Cutaneous T-cell Lymphoma Stage I, Cutaneous T-cell Lymphoma Stage II, Cutaneous T-cell Lymphoma Stage III, Cutaneous T-cell Lymphoma Stage IV
Conditions
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.
Interventions
DRUGvorinostat
Given PO
OTHERflow cytometry
correlative study
OTHERlaboratory biomarker analysis
correlative study
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * Prothrombin time or international normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN) unless receiving therapeutic anticoagulation * Partial thromboplastin time (PTT) =\< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation * Serum creatinine =\< 1.5 X ULN OR calculated creatinine clearance \>= 60 mL/min for patients with creatinine levels \> 1.5 X institutional ULN; creatinine clearance should be calculated per institutional standard * Serum total bilirubin =\< 2 X ULN * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic aminotransaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic aminotransaminase \[SGPT\]) =\< 3.0 X ULN * Alkaline Phosphatase (liver fraction) =\< 3.0 X ULN
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) * Presence of congestive heart failure (New York Heart Association \[NYHA\] class IV) or angina (NYHA class IV) or presence of a medically significant arrhythmia * Congenital long QT syndrome * Corrected QT interval \> 480 msec on screening electrocardiogram (ECG) * Presence of uncontrolled hypertension manifested by systolic blood pressure \>= 180 mmHg and/or diastolic blood pressure \>= 100 mmHg * Documented current active infection with human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, and/or cytomegalovirus (CMV) * Presence of uncontrolled bacterial or viral infection (subject may be receiving chronic antimicrobial therapy) * History of culture-documented bacteremia in the previous 2 weeks * Concurrent therapy with any histone deacetylase (HDAC)-like compound; patients treated with valproic acid for epilepsy may enroll after a 30 day washout period * Recent change (in the past 2 weeks) in the doses or regimens of medication used for any chronic non-oncologic conditions for reasons of worsening of chronic illness (change in doses of chronic medications associated with improvement in a chronic illness are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response | 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
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Up to 30 days post-treatment | Assessed by changes in the sum of the products in the greatest diameters of enlarged lymph nodes by serial computed tomography (CT) or positron emission tomography (PET)/CT scans. |
| Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Up to 30 days post-treatment | Toxicities will be graded in severity according to the guidelines outlined in the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0. |
| Number of Participants With Overall Response as Measured by Sezary Cell Count | Baseline to 30 days post-treatment | Overall response defined by a clinically significant decrease in Sezary cell count (\>50% decrease from baseline). |
| Changes in the Physicians Serial Assessment of Erythroderma Score | Baseline to 30 days post-treatment | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
vorinostat: Given PO
flow cytometry: correlative study
laboratory biomarker analysis: correlative study | 4 |
| 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.
vorinostat: Given PO
flow cytometry: correlative study
laboratory biomarker analysis: correlative study | 7 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort I (>=65 Years Old) | Cohort II (<65 Years Old) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 7 / 7 |
| serious Total, serious adverse events | 0 / 4 | 1 / 7 |
Outcome results
Primary
Objective Response
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.
Time frame: After at least 14 days. With Confirmation after additional 28 days.
Population: In cohort 1, only 3 of the 4 subjects consented were used for analysis. 1 patient in this cohort only completed 3 days of treatment before removing themselves from treatment and withdrawing consent. This patient was deemed inevaluable, as the timeframe for initial evaluation is 14 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I (>=65 Years Old) | Objective Response | 0 percentage of total |
| Cohort II (<65 Years Old) | Objective Response | 57 percentage of total |
Secondary
Changes in the Physicians Serial Assessment of Erythroderma Score
Time frame: Baseline to 30 days post-treatment
Population: 2 subjects \>= 65, 3 subjects \<= 65 with baseline erythroderma score.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort I (>=65 Years Old) | Changes in the Physicians Serial Assessment of Erythroderma Score | No change | 2 Participants |
| Cohort I (>=65 Years Old) | Changes in the Physicians Serial Assessment of Erythroderma Score | Reduction | 0 Participants |
| Cohort I (>=65 Years Old) | Changes in the Physicians Serial Assessment of Erythroderma Score | Resolution | 0 Participants |
| Cohort II (<65 Years Old) | Changes in the Physicians Serial Assessment of Erythroderma Score | No change | 0 Participants |
| Cohort II (<65 Years Old) | Changes in the Physicians Serial Assessment of Erythroderma Score | Reduction | 3 Participants |
| Cohort II (<65 Years Old) | Changes in the Physicians Serial Assessment of Erythroderma Score | Resolution | 2 Participants |
Secondary
Number of Participants With Overall Response as Measured by Sezary Cell Count
Overall response defined by a clinically significant decrease in Sezary cell count (\>50% decrease from baseline).
Time frame: Baseline to 30 days post-treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I (>=65 Years Old) | Number of Participants With Overall Response as Measured by Sezary Cell Count | Overall response | 2 participants |
| Cohort I (>=65 Years Old) | Number of Participants With Overall Response as Measured by Sezary Cell Count | Stable disease | 0 participants |
| Cohort II (<65 Years Old) | Number of Participants With Overall Response as Measured by Sezary Cell Count | Overall response | 1 participants |
| Cohort II (<65 Years Old) | Number of Participants With Overall Response as Measured by Sezary Cell Count | Stable disease | 3 participants |
Secondary
Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood);
Assessed by changes in the sum of the products in the greatest diameters of enlarged lymph nodes by serial computed tomography (CT) or positron emission tomography (PET)/CT scans.
Time frame: Up to 30 days post-treatment
Population: 7 subjects with nodal disease (2 subjects \>=65 and 5 subjects \<= 65: 1 not evaluable)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I (>=65 Years Old) | Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Overall Response | 0 participants |
| Cohort I (>=65 Years Old) | Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Stable Disease | 2 participants |
| Cohort I (>=65 Years Old) | Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Progressive Disease | 0 participants |
| Cohort II (<65 Years Old) | Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Overall Response | 0 participants |
| Cohort II (<65 Years Old) | Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Stable Disease | 3 participants |
| Cohort II (<65 Years Old) | Objective Response Rate of Extracutaneous Manifestations of CTCL (Lymph Node Enlargement, Sezary Cells in Peripheral Blood); | Progressive Disease | 1 participants |
Secondary
Occurrences of Dose Adjustment as Measured by Safety/Toxicity
Toxicities will be graded in severity according to the guidelines outlined in the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.
Time frame: Up to 30 days post-treatment
Population: 4 subjects \>= 65, 7 subjects \<= 65 who received at least one dose of drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I (>=65 Years Old) | Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Dose delay | 1 Occurrences |
| Cohort I (>=65 Years Old) | Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Dose reduction | 1 Occurrences |
| Cohort I (>=65 Years Old) | Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Treatment discontinuation | 1 Occurrences |
| Cohort II (<65 Years Old) | Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Dose delay | 2 Occurrences |
| Cohort II (<65 Years Old) | Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Dose reduction | 1 Occurrences |
| Cohort II (<65 Years Old) | Occurrences of Dose Adjustment as Measured by Safety/Toxicity | Treatment discontinuation | 0 Occurrences |