Lymphoma
Conditions
Brief summary
This is an investigational study that increases the dosage to determine the safety/tolerability, and efficacy of a histone deacetylase inhibitor in combination with Targretin in patients with cutaneous T-cell lymphoma in patients who have failed at least one prior systemic therapy.
Interventions
DRUGvorinostat
Dose escalation study starting with vorinostat 200 mg q.d. capsules (1 capsule daily) and rising up to vorinostat 400 mg q.d. capsules (1 capsule daily). Up to 6 months of treatment.
DRUGComparator: bexarotene
Dose escalation with bexarotene 150 mg/m2 capsules rising up to 300 mg/m2 capsules (1 capsule daily). Up to 6 months of treatment.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women or men greater than or equal to 18 years of age * Advanced cutaneous T-cell lymphoma, stage IB or higher including Sezary Syndrome with progressive, persistent, or recurrent disease * Failure of at least one systemic therapy, not including Bexarotene (Targretin) * Eastern Cooperative Oncology Group (ECOG) status less than or equal to 2 (measurement to determine your ability to perform daily activities)
Exclusion criteria
* Patient has had investigational treatment in the preceding 30 days * Active hepatitis B or C, history of HIV * Prior treatment with any HDAC inhibitor * Patients must be disease free from prior malignancies for greater than 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | Day 1 to day 28 | Number of patients with Dose Limiting Toxicities (DLT). A DLT is an adverse event that determined the treatment dose level was not tolerable for that patient in Cycle 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Responded to Treatment | Every 28 days for up to 6 Months of Treatment | Disease burden as assessed by the pre-specified Severity Weighted Assessment Tool (SWAT) measurement. A Response is defined as equal to or greater than 50% improvement in SWAT score. SWAT Score is determined by the Lesions classified as patch, plaque, or tumor. The sum of percent of total body surface area (%TBSA) by lesion type is derived and multiplied by a factor of 1 (for patch), 2 (for plaque), or 4 (for tumor). The skin score total is derived by summing the skin score subtotals for patches, plaques and tumors. The skin score total is dimensionless and can range from 0 to 400 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 150 milligrams/meter\[2\] daily x 7 days per week | 3 |
| Cohort 2 Vorinostat 300 milligrams daily for 7 days per week + Bexarotene 150 milligrams/meter\[2\] daily x 7 days per week | 5 |
| Cohort 2a Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 225 milligrams/meter\[2\] daily x 7 days per week | 3 |
| Cohort 2b Vorinostat 200 milligrams daily for 7 days per week + Bexarotene 300 milligrams/meter\[2\] daily x 7 days per week | 3 |
| Cohort 6 Vorinostat 400 milligrams daily for 7 days per week + Bexarotene 150 milligrams daily for 7 days per week | 5 |
| Cohort 7 Vorinostat 400 milligrams daily for 7 days per week + Bexarotene daily for 7 days per week \[150 milligrams (Cycle 1) 225 milligrams (Cycle 2-6)\] | 4 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Base Protocol | Adverse Event | 0 | 2 | 1 | 0 | 0 | 0 |
| Base Protocol | Lack of Efficacy | 1 | 0 | 0 | 0 | 2 | 0 |
| Base Protocol | Withdrawal by Subject | 1 | 2 | 1 | 0 | 0 | 1 |
| Continuation Phase | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 |
| Continuation Phase | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 |
| Continuation Phase | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 2a | Cohort 2b | Cohort 6 | Cohort 7 | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized 26-35 years of age | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Age, Customized 36-45 years of age | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Age, Customized 46-55 years of age | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 1 participants | 4 participants |
| Age, Customized 56-65 years of age | 1 participants | 1 participants | 1 participants | 2 participants | 3 participants | 1 participants | 9 participants |
| Age, Customized 66-75 years of age | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 2 participants | 4 participants |
| Age, Customized Over 75 years of age | 0 participants | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity Turkish | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity White | 3 participants | 5 participants | 3 participants | 2 participants | 5 participants | 4 participants | 22 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / — | 5 / — | 3 / — | 3 / — | 5 / — | 4 / — |
| serious Total, serious adverse events | 2 / — | 2 / — | 1 / — | 0 / — | 2 / — | 1 / — |
Outcome results
Primary
Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities
Number of patients with Dose Limiting Toxicities (DLT). A DLT is an adverse event that determined the treatment dose level was not tolerable for that patient in Cycle 1.
Time frame: Day 1 to day 28
Population: All Patients treated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | No DLT | 3 Participants |
| Cohort 1 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | DLT | 0 Participants |
| Cohort 2 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | No DLT | 3 Participants |
| Cohort 2 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | DLT | 2 Participants |
| Cohort 2a | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | No DLT | 3 Participants |
| Cohort 2a | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | DLT | 0 Participants |
| Cohort 2b | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | DLT | 0 Participants |
| Cohort 2b | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | No DLT | 3 Participants |
| Cohort 6 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | DLT | 0 Participants |
| Cohort 6 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | No DLT | 5 Participants |
| Cohort 7 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | No DLT | 2 Participants |
| Cohort 7 | Maximum Tolerated Dose (MTD) as Determined by the Number of Participants With Dose Limiting Toxicities | DLT | 1 Participants |
Secondary
Number of Participants Who Responded to Treatment
Disease burden as assessed by the pre-specified Severity Weighted Assessment Tool (SWAT) measurement. A Response is defined as equal to or greater than 50% improvement in SWAT score. SWAT Score is determined by the Lesions classified as patch, plaque, or tumor. The sum of percent of total body surface area (%TBSA) by lesion type is derived and multiplied by a factor of 1 (for patch), 2 (for plaque), or 4 (for tumor). The skin score total is derived by summing the skin score subtotals for patches, plaques and tumors. The skin score total is dimensionless and can range from 0 to 400
Time frame: Every 28 days for up to 6 Months of Treatment
Population: All patients treated
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Participants Who Responded to Treatment | Response | 0 Participants |
| Cohort 1 | Number of Participants Who Responded to Treatment | No Response | 3 Participants |
| Cohort 2 | Number of Participants Who Responded to Treatment | Response | 0 Participants |
| Cohort 2 | Number of Participants Who Responded to Treatment | No Response | 5 Participants |
| Cohort 2a | Number of Participants Who Responded to Treatment | Response | 0 Participants |
| Cohort 2a | Number of Participants Who Responded to Treatment | No Response | 3 Participants |
| Cohort 2b | Number of Participants Who Responded to Treatment | Response | 1 Participants |
| Cohort 2b | Number of Participants Who Responded to Treatment | No Response | 2 Participants |
| Cohort 6 | Number of Participants Who Responded to Treatment | Response | 2 Participants |
| Cohort 6 | Number of Participants Who Responded to Treatment | No Response | 3 Participants |
| Cohort 7 | Number of Participants Who Responded to Treatment | Response | 1 Participants |
| Cohort 7 | Number of Participants Who Responded to Treatment | No Response | 2 Participants |