Study of Pralatrexate With Vitamin B12 and Folic Acid in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PROPEL)

December 9, 2019 updated by: Acrotech Biopharma Inc.

A Multi-Center, Phase 2, Open-Label Study of (RS)-10-Propargyl-10-Deazaaminopterin (Pralatrexate) With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

Primary

• Determine the efficacy of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory peripheral T-cell lymphoma (PTCL)

Secondary

  • Determine the safety of pralatrexate with concurrent vitamin B12 and folic acid supplementation when administered to patients with relapsed or refractory PTCL
  • Determine the pharmacokinetic (PK) profile of pralatrexate when administered with vitamin B12 and folic acid supplementation

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

This is a Phase 2, single arm, non-randomized, open-label, multi-center study designed to evaluate the safety and effectiveness of pralatrexate when administered with vitamin B12 and folic acid supplementation to patients with relapsed or refractory PTCL.

Pralatrexate will be given over 3-5 minutes intravenously (IV), which means through a vein. If pralatrexate is tolerated well, the patient will receive IV injections of pralatrexate every week for 6 weeks, followed by 1 week without receiving pralatrexate. These 7 week cycles will be repeated depending on response and tolerability.

Study Type

Interventional

Enrollment (Actual)

115

Phase

  • Phase 2

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

      • Brussels, Belgium, 1200
        • Cliniques Universitaire Saint-Luc
      • Yvoir, Belgium, 5530
        • Cliniques Universitaires UCL
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
      • Creteil, France, 94010
        • CHU Henri Mondor
      • Dijon, France, 21034
        • CHU DIJON - Hôpital d'enfant
      • Nice, France, 06202
        • CHU Nice - Hôpital de l'Archet 1
      • Paris, France, 44093
        • CHU Nantes - Hôtel Dieu
      • Paris, France, 75475
        • CHU Saint Louis
      • Pierre-Benite, France, 69310
        • Centre Hospitalier Lyon Sud
      • Reims, France, 51092
        • CHU Robert Debré
      • Bologna, Italy, 40138
        • Ospedale Sant'Orsola - Policlinico Sant'Orsola
      • London, United Kingdom, SW17 ORE
        • St. Georges Hospital
      • Sutton, United Kingdom, SM2 5PT
        • The Royal Marsden NHS Foundation Trust
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Los Angeles, California, United States, 90095-7077
        • University of California at Los Angeles
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nevada
      • Las Vegas, Nevada, United States, 89135
        • Nevada Cancer Institute
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • The Cancer Center at Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10021
        • New York Presbyterian Hospital
      • Rochester, New York, United States, 14642
        • University of Rochester Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center

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:

  • Histologically/cytologically confirmed PTCL, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification:

    1. T/Natural Killer (T/NK) cell leukemia/lymphoma
    2. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
    3. Angioimmunoblastic T cell lymphoma
    4. Blastic Natural Killer (NK) lymphoma (with skin, lymph node, or visceral involvement)
    5. Anaplastic large cell lymphoma, primary systemic type
    6. PTCL - unspecified
    7. T/NK-cell lymphoma - nasal
    8. Enteropathy-type intestinal lymphoma
    9. Hepatosplenic T cell lymphoma
    10. Extranodal peripheral T/NK-cell lymphoma - unspecified
    11. Subcutaneous panniculitis T-cell lymphoma
    12. Transformed mycosis fungoides
  • Documented progression of disease after at least 1 prior treatment. Patients may not have received experimental therapy as their only prior therapy. Patient has at least 1 biopsy from initial diagnosis or in the relapsed setting to confirm the diagnosis of PTCL. Patient has recovered from the toxic effects of prior therapy. Patients treated with monoclonal antibody therapy may be enrolled regardless of the time frame of the therapy if they have progression of disease.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  • ≥ 18 years of age.
  • Adequate hematological, hepatic, and renal function.
  • Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Patients who are postmenopausal for at least 1 year or are surgically sterilized do not require this test.
  • Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate.
  • Patient has given written informed consent.

Exclusion Criteria:

  • Patient has:

    1. Precursor T/NK neoplasms, with the exception of blastic NK lymphoma
    2. T cell prolymphocytic leukemia (T-PLL)
    3. T cell large granular lymphocytic leukemia
    4. Mycosis fungoides, other than transformed mycosis fungoides
    5. Sézary syndrome
    6. Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis
  • Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease free for greater than or equal to 5 years.
  • Congestive heart failure Class III/IV according to the New York Heart Association's Heart Failure Guidelines.
  • Uncontrolled hypertension.
  • Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy.
  • Patient has, or history of, brain metastases or central nervous system (CNS) disease.
  • Patient has undergone an allogeneic stem cell transplant.
  • Patient has relapsed less than 75 days from time of an autologous stem cell transplant.
  • Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the patient to receive protocol treatment.
  • Major surgery within 2 weeks of study entry.
  • Receipt of any conventional chemotherapy or radiation therapy (RT) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.
  • Receipt of corticosteroids within 7 days of study treatment, unless patient has been taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.
  • Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
  • Previous exposure to pralatrexate.

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: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate Per Independent Central Review
Time Frame: Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Patient response to treatment was determined by independent central review using International Workshop Criteria (IWC). Results present the best overall response. The initial response assessment was scheduled at week 7 (prior to Cycle 2) and then prior to every even-numbered cycle (every 14 weeks) for up to two years after first dose.
Response was assessed at 7 weeks (prior to Cycle 2) and then prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response Per Independent Central Review
Time Frame: Measured from the first day of documented response, assessed at prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Calculated only for those pts with an objective response. Pts receiving subsequent therapy (including transplant) before progressive disease (PD) was documented were censored at date of last response assessment obtained prior to subsequent therapy, with a note indicating censoring occurrence & reason. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last evaluable assessment of response. Pts who withdrew from treatment prior to PD or initiation of subsequent therapy without withdrawing consent were followed for disease status when possible.
Measured from the first day of documented response, assessed at prior to every other even-numbered cycle (every 14 weeks) until disease progression or death for up to 2 years after initial dose
Progression-free Survival Per Independent Central Review
Time Frame: Calculated as the number of days from treatment day 1 to the date of disease progression or death, regardless of cause for up to 2 years after initial dose
Patients (pts) with subsequent therapy prior to PD were censored at date of last response assessment prior to subsequent therapy. Pts who were alive without PD were censored at the date of last assessment of first dose. Pts who withdrew consent to participate in the study prior to PD were censored at the date of their last disease assessment or treatment day 1. Pts who withdrew consent from treatment prior to PD without withdrawing consent for follow-up were followed for disease status & survival. Pts who did not have response assessments after baseline were censored at treatment day 1.
Calculated as the number of days from treatment day 1 to the date of disease progression or death, regardless of cause for up to 2 years after initial dose
Overall Survival Per Independent Central Review
Time Frame: Assessed every 14 weeks while on treatment, and after disease progression no less frequently than every 6 months for up to 2 years after first dose.
Calculated as date of death - date of enrollment +1, estimated using the product-limit estimator. Pts who had not died (no record of death) or were lost to follow-up were censored at the date of last contact. Pts who withdrew consent to participate in the study including consent to be followed, were censored on the date of withdrawal. Pts who withdrew from treatment without withdrawing consent were followed for survival status whenever possible.
Assessed every 14 weeks while on treatment, and after disease progression no less frequently than every 6 months for up to 2 years after first dose.

Collaborators and Investigators

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

Investigators

  • Study Chair: Owen O'Connor, MD, PhD, Columbia University

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

August 1, 2006

Primary Completion (ACTUAL)

January 1, 2009

Study Completion (ACTUAL)

February 24, 2009

Study Registration Dates

First Submitted

August 14, 2006

First Submitted That Met QC Criteria

August 15, 2006

First Posted (ESTIMATE)

August 16, 2006

Study Record Updates

Last Update Posted (ACTUAL)

December 19, 2019

Last Update Submitted That Met QC Criteria

December 9, 2019

Last Verified

December 1, 2019

More Information

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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