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

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”

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

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.

Intervention(s) in this Clinical Trial

• Drug: Pralatrexate Injection
  • Pralatrexate 30 mg/m2 via IV push over 3-5 minutes for 6 weeks in a 7 week cycle.

Primary 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
    Safety Issue?: No

Secondary 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
    Safety Issue?: No
• 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
    Safety Issue?: No
• 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.
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Allos Therapeutics Industry

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00364923

Study ID Number: PDX-008

ClinicalTrials.gov Identifier: NCT00364923

Health Authority: United States: Food and Drug Administration