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

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ClinicalTrials.gov Identifier: NCT02594267
Recruitment Status : Active, not recruiting
First Posted : November 3, 2015
Last Update Posted : September 25, 2019
Sponsor:
Collaborator:
Axis Clinicals Limited
Information provided by (Responsible Party):
Acrotech Biopharma LLC

Brief 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).

Condition or disease Intervention/treatment Phase
Peripheral T-Cell Lymphoma (PTCL) Drug: Pralatrexate Injection Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : October 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma Steroids

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 Name: Folotyn




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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.

  2. Objective Response Rate [ Time Frame: 126 Days ]
    To evaluate the Objective Response Rate (ORR) of 6 cycles of Fol-CHOP

  3. 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.

  4. Pharmacokinetics: Area Under the Curve (AUC) [ Time Frame: 126 Days ]
    Non-compartmental Analysis

  5. Pharmacokinetics: Maximum Concentration (Cmax) [ Time Frame: 126 Days ]
    Non-compartmental Analysis

  6. Pharmacokinetics: Time to Maximum concentration (Tmax) [ Time Frame: 126 Days ]
    Non-compartmental Analysis

  7. Pharmacokinetics: Clearance (CL) [ Time Frame: 126 Days ]
    Non-compartmental Analysis



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02594267


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
MD Anderson
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance/University of Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Acrotech Biopharma LLC
Axis Clinicals Limited
Investigators
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Study Director: Nawazish Khan, MD Acrotech Biopharma LLC

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Responsible Party: Acrotech Biopharma LLC
ClinicalTrials.gov Identifier: NCT02594267     History of Changes
Other Study ID Numbers: SPI-FOL-101
First Posted: November 3, 2015    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: July 2019
Keywords provided by Acrotech Biopharma LLC:
PTCL
Peripheral T-Cell Lymphoma
Folotyn
Pralatrexate
CHOP
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Prednisone
Cyclophosphamide
Doxorubicin
Vincristine
Aminopterin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents
Glucocorticoids