Official Title: “A Phase 1/2a Open-Label Study of Sequential Pralatrexate and Gemcitabine With Vitamin B12 and Folic Acid Supplementation in Patients With Relapsed or Refractory Lymphoproliferative Malignancies”

This is a Phase 1/2a, non-randomized, open-label, multi-center study designed to determine the Maximum Tolerated Dose (MTD) of Pralatrexate Injection and Gemcitabine with vitamin B12 and folic acid supplementation to patients with relapsed or refractory lymphoproliferative malignancies.

Study Type: Interventional

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

Study Primary Completion Date: November 2010

Intervention(s) in this Clinical Trial

• Drug: Pralatrexate Injection
  • Pralatrexate Injection will be administered via IV push and then followed by an infusion of Gemcitabine every other week. One cycle of treatment will be 4 weeks in duration. The total treatment duration will not exceed 12 months from first treatment.
• Drug: Gemcitabine hydrochloride (HCl)
  • Following Pralatrexate Injection administration, Gemcitabine will be administered via IV infusion every other week. One cycle of treatment will be 4 weeks in duration. The total treatment duration will not exceed 12 months from first treatment.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: PDX/Gem
  • Pralatrexate Injection and Gemcitabine

Primary Measures

• Phase 1: MTD and recommended phase 2 dose, safety and tolerability, and PK profile. Phase 2a: tolerability and preliminary efficacy (based on investigator assessment of response) in relapsed/refractory PTCL and B-Cell Lymphoma.
  • Time Frame: Study duration
    Safety Issue?: Yes

Inclusion Criteria:

• Diagnosis per the REAL WHO disease classification.
• Phase 1: Histologically/cytologically confirmed lymphoproliferative malignancy.
• Patients with Hodgkin's disease or non-Hodgkin's lymphoma are eligible, with the exceptions per exclusion criterion #1.
• Phase 2a: Histologically/cytologically confirmed PTCL or B-cell lymphoma, with the exceptions per exclusion criterion #1.
• Documented disease progression after at least 1 prior treatment, and progression after last prior treatment. Any number of prior therapies is allowed. Patient has recovered from the toxic effects of prior therapy. Patients treated with an FDA-approved monoclonal antibody therapy may be enrolled any time the therapy if they have progression of disease.
• ECOG Performance Status ≤ 2.
• At least 18 years of age.
• Adequate hematological, hepatic, and renal function, including: MMA < 200 nmol/L and Hcy < 10 μmol/L, or receipt of 1 mg oral folic acid daily for at least 10 days prior to planned start of pralatrexate & 1 mg intramuscular vitamin B12 within 10 weeks of the planned start of pralatrexate.
• Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment start 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.
• Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment start until at least 90 days after the last administration of pralatrexate.
• Given written informed consent.

Exclusion Criteria:

• Phase 1, B-cell:
• Lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia)
• Plasma cell myeloma/plasmacytoma
• Hairy cell leukemia
• Phase 2a, PTCL:
• Precursor T/NK neoplasms, except blastic NK lymphoma
• T-cell prolymphocytic leukemia
• T-cell large granular lymphocytic leukemia
• Mycosis fungoides, except transformed mycosis fungoides
• Sézary syndrome
• Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis
• Phase 2a, B-cell:
• Lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia)
• Plasma cell myeloma/plasmacytoma
• Hairy cell leukemia
• Relapsed Hodgkin's disease or diffuse large B-cell lymphoma patients who are candidates for high dose therapy and autologous stem cell transplantation and for whom it is a standard curative option.
• Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, must be disease-free for ≥ 5 years.
• NYHA Functional Classification congestive heart failure Class III/IV.
• Uncontrolled hypertension.
• HIV-positive diagnosis and is receiving combination anti-retroviral therapy.
• Central nervous system disease.
• Undergone allogeneic stem cell transplant.
• Relapsed < 100 days from time of an autologous stem cell transplant.
• Patients with disease refractory to peripheral blood stem cell transplant or who have relapsed < 100 days after transplant.
• Active uncontrolled infection or underlying medical condition including unstable cardiac disease, or other serious illness impairing the ability to receive protocol treatment.
• Major surgery within 2 weeks of planned start of treatment.
• Receipt of any conventional chemotherapy or radiation therapy (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 7 days of study treatment, unless on a continuous dose of ≤ 10 mg/day of prednisone for at least 1 month.
• Use of investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the study.
• Received a monoclonal antibody within 3 months without evidence of progression.
• Previous exposure to pralatrexate and/or gemcitabine if it was discontinued due to treatment-related toxicity.

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 M. Horwitz, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Overall Contact: Shannon Wilroy 303-426-6262 swilroy@allos.com

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00481871

Study ID Number: PDX-009

ClinicalTrials.gov Identifier: NCT00481871

Health Authority: United States: Food and Drug Administration