Official Title: “Protocol PDX-010: 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”

This is a Phase 1, single-arm, open-label, multi-center study designed to determine an effective and well-tolerated dose and schedule of pralatrexate when administered concurrently with vitamin B12 and folic acid supplementation to patients with relapsed or refractory CTCL.

One cycle of treatment will be 3 or 4 weeks in duration, depending on treatment group.

Treatment will continue until a patient meets criteria for discontinuation.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment

Study Primary Completion Date: December 2009

Intervention(s) in this Clinical Trial

• Drug: (RS)-10-Propargyl-10-Deazaaminopterin (pralatrexate)
  • 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.

Primary Measures

• To determine an effective and well-tolerated dose and schedule of pralatrexate with vitamin B12 and folic acid supplementation that can be administered safely to patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL).
  • Time Frame: Study duration
    Safety Issue?: Yes

Secondary Measures

• To characterize the safety profile of pralatrexate in this group of patients.
  • Time Frame: Study duration
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Patients with no curative treatment options available for their histologically and/or cytologically confirmed relapsed or refractory CTCL of the following subtypes:
• 1. Mycosis fungoides Stage IB or higher.
• 2. Sézary syndrome.
• 3. Primary cutaneous anaplastic large cell.
• 2. Documented progression or relapse of disease after at least 1 previous systemic therapy, defined as chemotherapy, oral bexarotene, vorinostat, interferon-α, denileukin diftitox, extracorporeal photochemotherapy (ECP), and anti-CD52 antibody (alemtuzumab). The patient should have clearly progressed after their last prior treatment regimen. The patient has recovered from the toxic effects of prior therapy.
• 3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• 4. Life expectancy ≥ 3 months.
• 5. ≥ 18 years of age.
• 6. Adequate hematological, hepatic, and renal function as defined by: absolute neutrophil count (ANC) ≥ 1,500/μL, platelet count ≥ 100,000/μL , (at both screening and within 3 days prior to planned dosing on cycle 1, dose 1), total bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), creatinine ≤ 1.5 mg/dL or if serum creatinine is elevated then patient has a calculated creatinine clearance ≥ 50 mL/min.
• 7. MMA serum concentration < 200 nmol/L and Hcy concentration < 10 μmol/L at screening or the patient has been on a regimen of 1 mg PO QD of folic acid for at least 10 days prior to the planned start of pralatrexate and has received 1 mg IM of vitamin B12 within 10 weeks of the planned start of pralatrexate.
• 8. 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. This test is not required for patients who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized. Pralatrexate should not be administered to women who are breastfeeding.
• 9. 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.
• 10. Patient has given written informed consent (IC) and privacy authorization (PA).

Exclusion Criteria:

• 1. 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.
• 2. Congestive heart failure Class III/IV according to the New York Heart Association's
• Heart Failure Guidelines.
• 3. Uncontrolled hypertension.
• 4. Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy.
• 5. Central nervous system (CNS) disease.
• 6. 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.
• 7. Patient has had major surgery within 2 weeks of planned start of treatment.
• 8. Receipt of any conventional chemotherapy or radiation therapy (RT) encompassing a substantial amount of bone marrow (> 10%) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.
• 9. Receipt of systemic corticosteroids within 3 weeks 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.
• 10. Initiation of or change in dosage of topical corticosteroids within 3 weeks of study treatment (topical steroid use within 3 weeks is allowed provided the strength and use has been stable for at least 1 month; topical corticosteroids cannot be started during the study).
• 11. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
• 12. Receipt of a monoclonal antibody within 3 months without evidence of progression.
• 13. Use of oral retinoids within 4 weeks of study treatment or high-dose vitamin A (once daily multi-vitamin allowed).
• 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

Steven Horwitz, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Overall Contact: Lacey Chance 303-426-6262 lchance@allos.com

Information obtained from ClinicalTrials.gov on September 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00554827

Study ID Number: PDX-010

ClinicalTrials.gov Identifier: NCT00554827

Health Authority: United States: Food and Drug Administration