A Dose-Finding Study of Folotyn® (Pralatrexate Injection) Plus CHOP With Peripheral T-Cell Lymphoma (PTCL)

July 23, 2021 updated by: Acrotech Biopharma Inc.

A Phase 1, Dose-Finding Study of Folotyn® (Pralatrexate Injection) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With Peripheral T-Cell Lymphoma (PTCL)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson
    • Washington
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance/University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 18 years or above
  2. Adequate hematologic, hepatic, and renal function
  3. Histologically confirmed, new diagnosis of PTCL
  4. Eligible for CHOP regimen
  5. Measurable disease based on Cheson 2007 criteria
  6. Eastern Cooperative Oncology Group (ECOG) performance status < 2
  7. Willing to perform at least two methods of contraception
  8. Negative pregnancy test of females with childbearing potential.

Exclusion Criteria:

  1. Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life threatening disease. If there is a history of prior malignancies or life threatening diseases, the patient must be disease free for at least 5 years.
  2. Congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification.
  3. Uncontrolled hypertension
  4. Central nervous system (CNS) metastases .
  5. Active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the patient to receive protocol treatment
  6. Major surgery within 30 days prior to enrollment.
  7. Use of any investigational drugs, biologics, or devices within 30 days prior or during the study treatment.
  8. Previous exposure to pralatrexate.
  9. Pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Part 1: Dose Finding, Cohort 1

Dose finding Phase Intervention: Folotyn (Pralatrexate Injection) CHOP: Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

The first cohort will begin with three patients with dose A of pralatrexate plus CHOP at full dose.

The second cohort will begin with three patients with dose B of pralatrexate plus CHOP at full dose.

The third cohort will begin with three patients with dose C of pralatrexate plus CHOP at full dose.

The fourth cohort will begin with three patients with dose D of pralatrexate plus CHOP at full dose.

The fifth cohort will begin with three patients with dose E of pralatrexate plus CHOP at full dose.

Part 2: Dose Expansion, Additional ten patients will be enrolled at the MTD or MAD (if the MTD is not reached) plus CHOP at full dose in this part of the study. Blood samples for PK analysis of pralatrexate will be collected at various intervals pre and post pralatrexate injection during cycle 1, Dose 1.
Drug: Pralatrexate Injection

Drug: Folotyn (Pralatrexate Injection)

CHOP : Cyclophosphamide, Doxorubicin, Vincristine, & Prednisone

Other Names:
  • Folotyn

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose
Time Frame: 126 Days
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)
126 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment emergent adverse events (TEAEs) using CTCAE version 4.03
Time Frame: 126 Days
Investigator will question the patient at every visit about AEs and intercurrent illnesses.
126 Days
Objective Response Rate
Time Frame: 126 Days
To evaluate the Objective Response Rate (ORR) of 6 cycles of Fol-CHOP
126 Days
Plasma concentration of pralatrexate in combination with CHOP
Time Frame: 126 Days
Measure the concentration of pralatrexate to evaluate the pharmacokinetics of pralatrexate when given in combination with CHOP using non-compartmental analysis.
126 Days
Pharmacokinetics: Area Under the Curve (AUC)
Time Frame: 126 Days
Non-compartmental Analysis
126 Days
Pharmacokinetics: Maximum Concentration (Cmax)
Time Frame: 126 Days
Non-compartmental Analysis
126 Days
Pharmacokinetics: Time to Maximum concentration (Tmax)
Time Frame: 126 Days
Non-compartmental Analysis
126 Days
Pharmacokinetics: Clearance (CL)
Time Frame: 126 Days
Non-compartmental Analysis
126 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Acrotech Biopharma Inc.

Collaborators

Axis Clinicals Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 10, 2015

Primary Completion (ACTUAL)

April 7, 2017

Study Completion (ACTUAL)

October 8, 2020

Study Registration Dates

First Submitted

September 25, 2015

First Submitted That Met QC Criteria

October 30, 2015

First Posted (ESTIMATE)

November 3, 2015

Study Record Updates

Last Update Posted (ACTUAL)

July 27, 2021

Last Update Submitted That Met QC Criteria

July 23, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPI-FOL-101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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