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

Peripheral T-Cell Lymphoma (PTCL) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02594267
• Other study ID #: SPI-FOL-101
• Status: Completed
• Phase: Phase 1
• Start date: November 10, 2015
• Est. completion date: October 8, 2020

Study information

• Verified date: July 2021
• Source: Acrotech Biopharma LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 8, 2020
• Est. primary completion date: April 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-Cell Lymphoma (PTCL)

Intervention

Drug:
• Pralatrexate Injection
Drug: Folotyn (Pralatrexate Injection) CHOP : Cyclophosphamide, Doxorubicin, Vincristine, & Prednisone

Locations

Country	Name	City	State
United States	MD Anderson	Houston	Texas
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Seattle Cancer Care Alliance/University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Acrotech Biopharma LLC	Axis Clinicals Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	126 Days
Secondary	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.	126 Days
Secondary	Objective Response Rate	To evaluate the Objective Response Rate (ORR) of 6 cycles of Fol-CHOP	126 Days
Secondary	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.	126 Days
Secondary	Pharmacokinetics: Area Under the Curve (AUC)	Non-compartmental Analysis	126 Days
Secondary	Pharmacokinetics: Maximum Concentration (Cmax)	Non-compartmental Analysis	126 Days
Secondary	Pharmacokinetics: Time to Maximum concentration (Tmax)	Non-compartmental Analysis	126 Days
Secondary	Pharmacokinetics: Clearance (CL)	Non-compartmental Analysis	126 Days