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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00364923
First received: August 14, 2006
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

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

Condition Intervention Phase
Peripheral T-cell Lymphoma
Drug: Pralatrexate Injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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. ] [ Designated as safety issue: No ]
    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.


Enrollment: 115
Study Start Date: August 2006
Estimated Study Completion Date: February 2012
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pralatrexate Injection
    Pralatrexate 30 mg/m2 via IV push over 3-5 minutes for 6 weeks in a 7 week cycle.
    Other Names:
    • FOLOTYN
    • Pralatrexate
    • Pralatrexate Solution for Infusion
    • (RS)-10-propargyl-10-deazaaminopterin
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00364923

  Show 32 Study Locations
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Chair: Owen O'Connor, MD, PhD Columbia University
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00364923     History of Changes
Other Study ID Numbers: PDX-008, 2006-002811-29
Study First Received: August 14, 2006
Results First Received: October 23, 2009
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Peripheral T-cell Lymphoma
T-cell Lymphoma
Lymphoma
PDX
Pralatrexate
Vitamin B12
Folic acid

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
10-deazaaminopterin
Aminopterin
Folic Acid
Hydroxocobalamin
Vitamin B 12
Vitamin B Complex
Vitamins
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014