Study of Pralatrexate & Gemcitabine With B12 & Folic Acid to Treat Relapsed/Refractory Lymphoproliferative Malignancies

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

This study is for patients with lymphoproliferative malignancies that have progressed after receiving a previous treatment (relapsed) or are no longer responding to treatment (refractory). To be in this study, patients must have certain types of Hodgkin's lymphoma (HL), peripheral T-cell lymphoma (PTCL), or B-cell lymphoma, including Waldenstrom's macroglobulinemia.

This study is being done to find doses of the combination of pralatrexate and gemcitabine with vitamin B12 and folic acid that can be safely given to patients with these types of lymphoma and explore the effectiveness of the treatment.

Intervention(s) in this Clinical Trial

• Drug: Pralatrexate Injection
  • Intravenous (IV) push administration over 30 seconds to 5 minutes into a patent IV line containing normal saline (0.9% sodium chloride). Sequential Dosing: 10 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 15 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.
• Drug: Gemcitabine Hydrochloride
  • Gemcitabine will be prepared and administered as an IV infusion as per manufacturer instructions. Sequential Dosing: 400 mg/m2 every 2 weeks (days 2 and 16) of a 4-week cycle until criteria for discontinuation per the protocol are met. Same Day Dosing: 600 mg/m2 every 2 weeks (days 1 and 15) of a 4-week cycle until criteria for discontinuation per the protocol are met.
• Dietary Supplement: Vitamin B12
  • 1 mg intramuscular injection Administered within 10 weeks of enrollment, every 8-10 weeks throughout the study and for at least 30 days after last dose of pralatrexate.
• Dietary Supplement: Folic Acid
  • 1 mg orally Administered daily for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days after last dose of pralatrexate.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Pralatrexate & Gemcitabine - Sequential Days
• Experimental: Pralatrexate & Gemcitabine - Same Day

Primary Measures

• Determine Pharmacokinetic (PK) Profile & Confirm Tolerability of Pralatrexate and Gemcitabine when Administered with Vitamin B12 and Folic Acid (for Phase 2 Patients)
  • Time Frame: Samples collected for Cycle 1, Doses 1 & 2
    Safety Issue?: Yes

Secondary Measures

• Best Overall Response
  • Time Frame: Assessed every 8 weeks (+/- 1 week)
    Safety Issue?: No

Inclusion Criteria:

• Phase 1: Histologically/cytologically confirmed lymphoproliferative malignancy.
• Patients with Hodgkin lymphoma (HL) or non-HL are eligible, with exceptions per exclusion criteria.
• Phase 2a: Histologically/cytologically confirmed HL, peripheral T-cell lymphoma (PTCL), or B-cell lymphoma including Waldenström's macroglobulinemia, with exceptions per exclusion criteria.
• Progression of disease (PD) after at least 1 prior treatment (any number of prior therapies allowed). PD after last prior treatment and recovered from toxic effects of prior therapy. Patients treated with an FDA-approved monoclonal antibody therapy may be enrolled at any time after the therapy if they have PD.
• PTCL patients must have received single-agent pralatrexate as a prior therapy.
• Eastern Cooperative Oncology Group performance status ≤ 2.
• Adequate blood, liver and kidney function per laboratory tests.
• Has taken 1 mg daily oral folic acid for at least 7 days prior to planned start of pralatrexate and received 1 mg vitamin B12 intramuscularly within 10 weeks of the planned start of pralatrexate.
• Females of childbearing potential must practice a medically acceptable contraceptive regimen from first dose until at least 30 days after last dose of pralatrexate and have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Postmenopausal (defined as greater than 12 months since last menses) and surgically sterilized females do not require this test.
• Males who are not surgically sterile must practice a medically acceptable contraceptive regimen from first dose until at least 90 days after last dose of pralatrexate.
• Give written informed consent.

Exclusion Criteria:

• Phase 1
• 1. B-cell: lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia); plasma cell myeloma/plasmacytoma; hairy cell leukemia.
• Phase 2a
• 1. PTCL: precursor T/Natural Killer (NK) neoplasms, with the exception of blastic
• NK lymphoma; T-cell prolymphocytic leukemia; T-cell large granular lymphocytic leukemia; mycosis fungoides (MF), except transformed MF; Sézary syndrome;
• primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis.
• 2. B-cell: plasma cell myeloma/plasmacytoma; hairy cell leukemia.
• Relapsed HL or diffuse large B-cell lymphoma patients who are candidates for high dose therapy and autologous stem cell transplantation (SCT) 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 at least 5 years.
• Congestive heart failure Class III/IV.
• Uncontrolled hypertension.
• Human immunodeficiency virus (HIV)- positive diagnosis with CD4 less than 100 or detectable viral load within past 3 months and receiving anti-retroviral therapy.
• Hepatitis B or C virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
• Central nervous system disease.
• Undergone an allogeneic SCT.
• Patients with disease refractory to peripheral blood SCT, or who have relapsed less than 100 days since an autologous or peripheral blood SCT.
• Active uncontrolled infection, underlying medical condition including unstable heart 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 greater than 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 no more than 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 PD.
• Previous exposure to pralatrexate and/or gemcitabine if 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 Investigator: Allos Therapeutics Industry

Overall Clinical Trial Officials and Contacts

Michael Saunders, MD Study Director Allos Therapeutics  

Information obtained from ClinicalTrials.gov on February 12, 2012

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