Lymphoma
Conditions
Brief summary
Part I evaluates the safety, tolerability and pharmacokinetics (PK) of vorinostat in Japanese patients with relapsed or refractory CTCL. Part II evaluates the safety of vorinostat in Japanese pts. with relapsed or refractory CTCL. Relapsed or refractory CTCL patients will be newly enrolled in Part II.
Interventions
DRUGvorinostat
Parts I & II: Vorinostat (400 mg) Oral, daily (QD). Treatment period is 28 days per cycle.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Parts I & II): * Patients With CTCL Who Have Progressive, Persistent Or Recurrent Disease Subsequent To At Least One Prior Therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status Must Be 0-2 * Patients Have Adequate Bone Marrow, Liver Function And Renal Function
Exclusion criteria
(Parts I & II): * Patients Had Prior Therapy Within 3 Weeks Before Registration, Or Have Not Recovered From Toxicities Of Prior Therapy * Patients Have Uncontrolled Intercurrent Illness * Pregnant Or Women Have A Will To Be Pregnant And Lactating Woman
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE) | Day 1 up until 30 days post study completion or early termination (up to approximately 506 days) | A laboratory AE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body. |
| Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT) | Day 1 to Day 28 | A DLT was defined as any of the following (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0): * Grade 3 (severe)-4 (life-threatening) neutropenia with fever ≥ 38.5ºC * Grade 3-4 neutropenia with an infection requiring antibiotic or antifungal treatment * Grade 4 neutropenia lasting at least 5 days * Grade 4 thrombocytopenia * Other Grade 4 hematologic toxicity, including a decrease in hemoglobin, only at the discretion of the principal investigator * Grade 3 or 4 non-hematologic event, except which are manageable by supportive care or non-prohibited therapies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours]) | Days 1 & 28 of Cycle 1 | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. |
| Part I: Maximum Drug Concentration (Cmax) | Days 1 & 28 of Cycle 1 | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. |
| Part I: Time at Which Cmax Occurs (Tmax) | Days 1 & 28 of Cycle 1 | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. |
| Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2) | Days 1 & 28 of Cycle 1 | Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vorinostat Parts I & II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 2 | 3 |
| Overall Study | Progressive Disease | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Vorinostat |
|---|---|
| Age, Continuous | 55.5 years STANDARD_DEVIATION 12 |
| Region of Enrollment Japan | 10 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT)
A DLT was defined as any of the following (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0): * Grade 3 (severe)-4 (life-threatening) neutropenia with fever ≥ 38.5ºC * Grade 3-4 neutropenia with an infection requiring antibiotic or antifungal treatment * Grade 4 neutropenia lasting at least 5 days * Grade 4 thrombocytopenia * Other Grade 4 hematologic toxicity, including a decrease in hemoglobin, only at the discretion of the principal investigator * Grade 3 or 4 non-hematologic event, except which are manageable by supportive care or non-prohibited therapies
Time frame: Day 1 to Day 28
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vorinostat | Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT) | 1 participants |
Primary
Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE)
A laboratory AE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body.
Time frame: Day 1 up until 30 days post study completion or early termination (up to approximately 506 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vorinostat | Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE) | Clinical AEs | 10 participants |
| Vorinostat | Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE) | Laboratory AEs | 6 participants |
Secondary
Part I: Maximum Drug Concentration (Cmax)
Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time frame: Days 1 & 28 of Cycle 1
Population: Number of participants with samples at the specified time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Vorinostat | Part I: Maximum Drug Concentration (Cmax) | Day 1 (n=6) | 0.83 µM | Standard Deviation 0.37 |
| Vorinostat | Part I: Maximum Drug Concentration (Cmax) | Day 28 (n=5) | 1.17 µM | Standard Deviation 0.37 |
Secondary
Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2)
Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time frame: Days 1 & 28 of Cycle 1
Population: Number of participants with samples at the specified time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Vorinostat | Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2) | Day 1 (n=5) | 1.94 hours | Standard Deviation 1.3 |
| Vorinostat | Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2) | Day 28 (n=4) | 2.30 hours | Standard Deviation 1.1 |
Secondary
Part I: Time at Which Cmax Occurs (Tmax)
Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time frame: Days 1 & 28 of Cycle 1
Population: Number of participants with samples at the specified time point
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Vorinostat | Part I: Time at Which Cmax Occurs (Tmax) | Day 1 (n=6) | 2.91 hours |
| Vorinostat | Part I: Time at Which Cmax Occurs (Tmax) | Day 28 (n=5) | 3.73 hours |
Secondary
Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours])
Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time frame: Days 1 & 28 of Cycle 1
Population: Number of participants with samples at the specified time point
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Vorinostat | Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours]) | Day 1 (n=6) | 4.59 µM*hr | Standard Deviation 2.34 |
| Vorinostat | Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours]) | Day 28 (n=5) | 5.59 µM*hr | Standard Deviation 1.24 |