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

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2009

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 Peripheral T-Cell Lymphoma.

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: (RS)-10-Propargyl-10-Deazaaminopterin
  • Pralatrexate will be administered for 6 weeks in a 7 week cycle. It is administered via IV push over 3-5 minutes.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Pralatrexate

Primary Measures

• The primary efficacy endpoint is response rate, and the secondary endpoints are duration of response, progression-free survival (PFS), and overall survival.
  • Time Frame: Study Duration
    Safety Issue?: No

Inclusion Criteria:

• 1. Patient has histologically/cytologically confirmed PTCL, using the Revised European

American Lymphoma (REAL) World Health Organization (WHO) disease classification:

• 1. T/Natural Killer (NK) cell leukemia/lymphoma
• 2. Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+)
• 3. Angioimmunoblastic T cell lymphoma
• 4. Blastic 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
• 2. Patient has 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.
• 3. Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
• 4. At least 18 years of age.
• 5. Adequate hematological, hepatic, and renal function as defined by: absolute neutrophil count (ANC) greater than or equal to 1000/mL, platelet count greater than or equal to 100,000/mL, total bilirubin less than or equal to 1.5 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper limit of normal (ULN) (AST/ALT < 5 x ULN if documented hepatic involvement with lymphoma), creatinine less than or equal to 1.5 mg/dL or a calculated creatinine clearance greater than or equal to 50 mL/min.
• 6. 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 (> 12 months since last menses) or are surgically sterilized do not require this test.
• 7. 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.
• 8. Patient has given written informed consent (IC).

Exclusion Criteria:

• 1. 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
• 2. 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.
• 3. Congestive heart failure Class III/IV according to the New York Heart Association's
• Heart Failure Guidelines.
• 4. Uncontrolled hypertension.
• 5. Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy.
• 6. Patient has, or history of, brain metastases or central nervous system (CNS) disease.
• 7. Patient has undergone an allogeneic stem cell transplant.
• 8. Patient has relapsed less than 75 days from time of an autologous stem cell transplant.
• 9. 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.
• 10. Patient has had major surgery within 2 weeks of study entry.
• 11. 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.
• 12. 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.
• 13. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
• 14. 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 Sponsor: Allos Therapeutics

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on October 10, 2008

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

Study ID Number: PROPEL

ClinicalTrials.gov Identifier: NCT00364923

Health Authority: United States: Food and Drug Administration