The purpose of this study is to evaluate the Maximum Tolerated Dose (MTD) of pralatrexate in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed peripheral T-cell lymphoma (PTCL).
This is a Phase 1, open-label, multicenter, two-part, dose-finding, dose-escalation study. The study is divided into two parts: Part 1 Up to five sequential dose cohorts will enroll a maximum of 6 patients each. Escalation of the pralatrexate dose, after CHOP administration (Fol-CHOP), will continue in a traditional 3+3 design, until determination of the MTD. If the MTD is not reached, the Maximum Administered Dose (MAD) of pralatrexate in combination with CHOP will be 30 mg/m2 IV on Days 1 and 8 of each 21-day cycle for up to 6 cycles. The first cohort will begin with three patients with dose A and CHOP at full dose. If none of the first three patients experiences a Dose-Limiting Toxicity (DLT), the next three patients will be enrolled in next higher dose cohort. If one of the first three patients in the first cohort experiences DLTs, an additional three patients will be enrolled into that cohort. If 2 or 3 of the first 3 patients experience DLTs, then the MTD is not found. For cohorts 2, 3, 4, and 5, If none of the first three patients experiences a DLT, the next three patients will be enrolled in next higher dose cohort. If one of the first three patients in the first cohort experiences DLTs, an additional three patients will be enrolled into that cohort. If 2 or 3 of the first 3 patients experience DLTs, then the previous cohort will be considered the MTD and up to an additional 10 patients will be enrolled at that dose in Part 2 of the study. Part 2 Once the MTD for the Fol-CHOP regimen has been established in Part 1 of the study, an additional 10 patients will be treated at the MTD (or MAD if MTD not reached) to confirm tolerability. Additionally, the PK of the established MTD of pralatrexate, when administered with CHOP at full dose, will be evaluated in these 10 patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Drug: Folotyn (Pralatrexate Injection) CHOP : Cyclophosphamide, Doxorubicin, Vincristine, \& Prednisone
Mayo Clinic
Rochester, Minnesota, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
MD Anderson
Houston, Texas, United States
Seattle Cancer Care Alliance/University of Washington
Seattle, Washington, United States
Maximum Tolerated Dose
To evaluate the Maximum Tolerated Dose (MTD) of pralatrexate in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen in patients with newly diagnosed peripheral T-cell lymphoma (PTCL)
Time frame: 126 Days
Number of participants with treatment emergent adverse events (TEAEs) using CTCAE version 4.03
Investigator will question the patient at every visit about AEs and intercurrent illnesses.
Time frame: 126 Days
Objective Response Rate
To evaluate the Objective Response Rate (ORR) of 6 cycles of Fol-CHOP
Time frame: 126 Days
Plasma concentration of pralatrexate in combination with CHOP
Measure the concentration of pralatrexate to evaluate the pharmacokinetics of pralatrexate when given in combination with CHOP using non-compartmental analysis.
Time frame: 126 Days
Pharmacokinetics: Area Under the Curve (AUC)
Non-compartmental Analysis
Time frame: 126 Days
Pharmacokinetics: Maximum Concentration (Cmax)
Non-compartmental Analysis
Time frame: 126 Days
Pharmacokinetics: Time to Maximum concentration (Tmax)
Non-compartmental Analysis
Time frame: 126 Days
Pharmacokinetics: Clearance (CL)
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Non-compartmental Analysis
Time frame: 126 Days