Study of Pralatrexate in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00554827
First received: November 5, 2007
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

This study is being conducted to identify how much and how often pralatrexate, given with vitamin B12 and folic acid, can be given safely to patients with cutaneous T-cell lymphoma (CTCL) that has relapsed (returned after responding to previous treatment) or is refractory (has not responded to previous treatment). It is also being conducted to get information on whether or not pralatrexate is effective in treating relapsed or refractory CTCL.


Condition Intervention Phase
Cutaneous T-cell Lymphoma
Drug: Pralatrexate Injection
Dietary Supplement: Vitamin B12
Dietary Supplement: Folic Acid
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label Study of Pralatrexate With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Determine an Effective and Well-tolerated Dose and Schedule of Pralatrexate with Vitamin B12 and Folic Acid Supplementation for Patients with Relapsed or Refractory Cutaneous T-cell Lymphoma (CTCL) [ Time Frame: Assessed at the end of every even-numbered cycle (every 8 weeks) for the first 6 months, then every 4 cycles (16 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Characterize the Safety Profile of Pralatrexate in Patients with Relapsed or Refractory CTCL. [ Time Frame: Assessed at all study visits: weekly while on treatment and at safety follow-up (35 +/- 5 days post-last dose) or early termination visit (at time of withdrawal) ] [ Designated as safety issue: Yes ]

Enrollment: 55
Study Start Date: August 2007
Study Completion Date: February 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pralatrexate Injection

    Intravenous (IV) push over 3-5 minutes into a patent IV line containing normal saline (0.9% sodium chloride).

    Pralatrexate will be administered via intravenous (IV) push over 3-5 minutes. The frequency of pralatrexate will be administered weekly for 3 or 4 weeks (depending on cohort), with 1 week of rest.

    Other Names:
    • FOLOTYN
    • PDX
    • Pralatrexate
    • (RS)-10-propargyl-10-deazaaminopterin
    Dietary Supplement: Vitamin B12

    1 mg intramuscular injection

    Administered at least 10 days prior to start of pralatrexate if patient has elevated methylmalonic acid (MMA) and/or homocysteine(Hcy) levels.

    Administered every 8-10 weeks throughout the study and for at least 30 days after last dose of pralatrexate.

    Other Name: Cyanocobalamin
    Dietary Supplement: Folic Acid

    1 mg orally

    Administered at least 10 days prior to start of pralatrexate if patient has elevated methylmalonic acid (MMA) and/or homocysteine(Hcy) levels.

    Administered daily throughout the study and for at least 30 days after last dose of pralatrexate.

    Other Names:
    • Vitamin B9
    • Folate
    • Folacin
  Eligibility

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

Inclusion Criteria:

  • Confirmed relapsed or refractory cutaneous T-cell lymphoma (CTCL):

    1. Mycosis fungoides Stage IB or higher
    2. Sézary syndrome
    3. Primary cutaneous anaplastic large cell
  • No curative treatment options.
  • Progression of disease (PD) or relapse of disease after at least 1 previous systemic therapy, PD after last prior treatment regimen, and recovered from the toxic effects of prior therapy.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  • Life expectancy ≥ 3 months.
  • Adequate blood, liver, and kidney function as determined by laboratory tests.
  • Methylmalonic acide (MMA) serum concentration < 200 nmol/L and homocysteine (Hcy) concentration < 10 μmol/L at screening, or receipt of 1 mg daily oral folic acid for at least 10 days prior to the planned start of pralatrexate and 1 mg intramuscular vitamin B12 within 10 weeks of the planned start of pralatrexate.
  • Women of childbearing potential must use a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last dose of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Serum pregnancy test not required for patients who are postmenopausal (greater than 12 months since last menses) or are surgically sterilized.
  • Women who are breastfeeding.
  • Men who are not surgically sterile must use a medically acceptable contraceptive regimen from start of pralatrexate until at least 90 days after the last administration of pralatrexate.
  • Written informed consent and privacy authorization.

Exclusion Criteria:

  • 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 ≥ 5 years. Patients with other prior malignancies < 5 years before study entry may be enrolled if treatment resulted in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease.
  • Congestive heart failure Class III/IV per the New York Heart Association Heart Failure Guidelines.
  • Uncontrolled hypertension.
  • Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of <100 mm3 or detectable viral load within the past 3 months, and is receiving combination anti-retroviral therapy.
  • Symptomatic central nervous system metastases or lesions for which treatment is required.
  • Active uncontrolled infection, underlying medical condition that would impair ability to receive protocol treatment.
  • Major surgery within 2 weeks of planned start of treatment.
  • Receipt of any conventional chemotherapy or radiation therapy (RT) encompassing >10% of bone marrow within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the study.
  • Receipt of systemic corticosteroids within 3 weeks of study treatment, unless on a continuous dose of ≤10 mg/day of prednisone for at least 1 month.
  • Initiation of or change in dosage of topical corticosteroids within 3 weeks of study treatment (topical steroid use within 3 weeks is allowed if strength/use has been stable for at least 1 month; topical corticosteroids cannot be started during the study).
  • Use of investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the study.
  • Receipt of a monoclonal antibody within 3 months without evidence of progression.
  • Use of oral retinoids within 4 weeks of study treatment or high-dose vitamin A.
  • Previous exposure to pralatrexate, unless the patient was on this study, achieved a complete or partial response, and was taken off study treatment because of investigator decision, and subsequently experienced disease recurrence or progressive disease.
  • Re-entering patients: must not have received subsequent therapy for CTCL during the time off initial study treatment.
  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: NCT00554827

Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
Stanford University School of Medicine
Redwood City, California, United States, 94063
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06519
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10017
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77080-4009
United States, Washington
Fred Hutchinson Cancer Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Michael Saunders, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00554827     History of Changes
Other Study ID Numbers: PDX-010
Study First Received: November 5, 2007
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Relapsed or Refractory Cutaneous T-cell Lymphoma
Lymphoma
Cutaneous T-cell Lymphoma
T-cell Lymphoma
Mycosis fungoides
Sézary syndrome
Primary cutaneous anaplastic large cell

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

ClinicalTrials.gov processed this record on July 28, 2014