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

NCT ID: NCT00481871

Last Updated: 2020-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2011-08-31

Brief Summary

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.

Conditions

Relapsed or Refractory Lymphoproliferative Malignancies; Hodgkin's Lymphoma; Peripheral T-cell Lymphoma; B-cell Lymphoma; Waldenstrom's Macroglobulinemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pralatrexate & Gemcitabine - Sequential Days

Group Type: EXPERIMENTAL

Pralatrexate Injection

Intervention Type: DRUG

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.

Gemcitabine Hydrochloride

Intervention Type: DRUG

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.

Vitamin B12

Intervention Type: DIETARY_SUPPLEMENT

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.

Folic Acid

Intervention Type: DIETARY_SUPPLEMENT

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.

Pralatrexate & Gemcitabine - Same Day

Group Type: EXPERIMENTAL

Pralatrexate Injection

Intervention Type: DRUG

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.

Gemcitabine Hydrochloride

Intervention Type: DRUG

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.

Vitamin B12

Intervention Type: DIETARY_SUPPLEMENT

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.

Folic Acid

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

FOLOTYN; PDX; Pralatrexate; (RS)-10-propargyl-10-deazaaminopterin; Gemcitabine; Gemzar®, Eli Lilly and Company; Gemcitabine Hydrochloride (HCl) for Injection; Cyanocobalamin; Vitamin B9; Folate; Folacin

Eligibility Criteria

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.

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acrotech Biopharma Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Saunders, MD

Role: STUDY_DIRECTOR

Spectrum Pharmaceuticals, Inc

Locations

University of California at Los Angeles

Los Angeles, California, United States

Stanford University School of Medicine

Stanford, California, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

University of Chicago Hospital

Chicago, Illinois, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

New York University Hospital

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

UT MD Anderson Cancer Center

Houston, Texas, United States

Cancer Therapy & Research Center

San Antonio, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

PDX-009

Identifier Type: -

Identifier Source: org_study_id