This study is designed to determine the recommended dose, safety, pharmacokinetics, and early efficacy of the combination of pralatrexate plus oral bexarotene in patients with relapsed or refractory CTCL.
This is a multi-center, dose-finding, Phase 1 study of pralatrexate plus bexarotene in patients who have relapsed or refractory CTCL. Primary Objective(s): • Determine the maximum tolerated dose (MTD) and recommended dose of pralatrexate plus bexarotene with concurrent vitamin B12 and folic acid supplementation when administered to patients who have failed prior systemic treatment. Secondary Objective(s): * Determine the safety profile of pralatrexate plus bexarotene when administered to patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). * Collect preliminary efficacy data. * Determine the pharmacokinetic (PK) profile of pralatrexate plus bexarotene in patients who underwent plasma PK sampling
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Intravenous (IV) push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride). 10 or 15 mg/m2, depending on cohort assignment. Dose reductions allowed for protocol-specified criteria. Administered weekly for 3 weeks of 4-week cycle (weekly for 3 weeks with one week of rest) until criteria for discontinuation per the protocol are met.
150 or 300 mg orally, depending on cohort assignment. Provided as 75 mg capsules and taken with a meal. Dose reductions allowed for protocol-specified criteria and implemented per the Targretin® package insert. Administered daily until criteria for study treatment discontinuation per the protocol are met.
Stanford University School of Medicine
Stanford, California, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center
Houston, Texas, United States
Dose Limiting Toxicity (DLT) Rate
DLT rate is the number of patients experiencing a DLT divided by number of evaluable patients and it will be summarized by dose level.
Time frame: Assessed weekly through cycle 1 (weeks 1-4)
Overall Response Rate (ORR)
best overall response is the best response recorded from the start of treatment until PD. The objective response rate is the proportion of patients with a best overall response of either CR or PR and it will be summarized by dose level and overall.
Time frame: Assessed after every 2 cycles (8 weeks) for the first 12 months, then every 4 cycles (16 weeks) until progression of disease.
Number of Patients with Treatment-related Adverse Events (AEs) and Serious AEs (SAEs)
(CTCAE) Scale, Version 4.0 for AE grading. * Grade 3 neutropenia lasting for ≥ 7 days or granulocyte colony-stimulating factor (G-CSF) administered. * Grade 3 thrombocytopenia. * Grade 3 treatment-related hyperlipidemia or hypothyroidism * Grade 3 study treatment-related non-hematologic toxicity
Time frame: Recorded at all study visits: weekly (every 7 +/- 2 days) while on treatment and at safety follow-up (35 +/- 5 days post-last dose) or early termination visit (at time of withdrawal).
Pharmacokinetic Parameters
This was collected during the dose-finding stage of the study. PK sampling is not included in the cohort expansion.
Time frame: Sampling through 24 hours post end-injection of pralatrexate in cycle 1 dose 1 (week 1) and cycle 1 dose 3 (week 3).
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1 mg intramuscular injection Administered within 10 weeks prior to start of study treatment, every 8-10 weeks throughout the study and for 30 days after last study treatment (dose of pralatrexate or bexarotene).
1-1.25 mg orally Administered daily for at least 7 days prior to start of study treatment, throughout the study and for 30 days after last study treatment (dose of pralatrexate or bexarotene).
Ospedale Sant'Orsola - Policlinico Sant'Orsola
Bologna, Italy