This is a Phase I Trial to assess the feasibility of Romidepsin combined with Brentuximab Vedotin for patients requiring Systemic Therapy for Cutaneous T-cell Lymphoma.
This is a traditional "3+3" phase 1 dose de-escalation design testing up to 3 dose levels of romidepsin in conjunction with brentuximab vedotin in patients with untreated or previously treated (up to 2 prior systemic regimens, including photopheresis) CTCL. Dose-limiting toxicities (DLT) will be determined during cycle 1. The first 3 subjects will begin at dose level 1. If no DLT is encountered another 3 subjects will be enrolled at the same dose level. The maximum tolerated dose (MTD) will be the dose level at which ≤ 1 of 6 of subjects experience DLT. If more than one subject at any one dose level encounters a DLT, the dose will be de-escalated for all subsequent subjects. Should no DLTs occur, the investigators will not escalate beyond dose level 1. Once the MTD has been confirmed, the investigators will enroll an additional 9 patients in a toxicity refinement cohort for a total of 15 evaluable patients at the MTD. Treatment will continue for up to 16 cycles (one cycle is 28 days) or until disease progression or toxicities, whichever occurs first. Drugs can be continued after 16 cycles if a patient has derived a clinical benefit from treatment after discussion with the sponsor-investigator.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Romidepsin at the dosage 10mg/m2 or 14mg/m2 will be given ONCE 14 days prior to cycle one and then on days 1,8,15 in each cycle. Each cycle is 28 days and treatment will continue up to 16 cycles
Brentuximab vedotin at the dosage 0.9mg/kg or 1.2 mg/kg will be given on days 1 and 15 in each cycle. Each cycle is 28 days and treatment will continue up to 16 cycles
University of Pennsylvania, Perelman Center
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Maximum tolerated dose (MTD)
CTCAE v4.03
Time frame: during treatment period which is an average of 64 weeks.
Dose-limiting toxicities (DLTs)
CTCAE v4.03
Time frame: during the first 28 days (cycle 1) of treatment
overall safety and tolerability of the combination of brentuximab vedotin & romidepsin assessed by adverse events.
CTCAE v4.03
Time frame: from start of treatment to 30 days post treatment period (16 cycles)
Estimate complete and partial response rate of the combination treatment
mSWAT skin assessment
Time frame: 64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years
Estimate complete and partial response rate of the combination treatment
Global Response Score (GRS).
Time frame: 64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years
Overall survival (OS)
OS is measured by length of time
Time frame: From the time of patient registration until death, measured every 12 weeks up to 2 years
Progression free survival (PFS)
PFS is measured in length of time by RECIST v1.1
Time frame: From the time of patient registration until disease progression, measured every 12 weeks up to 2 years
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