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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT00481871
First received: June 1, 2007
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Relapsed or Refractory Lymphoproliferative Malignancies
Hodgkin's Lymphoma
Peripheral T-cell Lymphoma
B-cell Lymphoma
Waldenstrom's Macroglobulinemia
Drug: Pralatrexate Injection
Drug: Gemcitabine Hydrochloride
Dietary Supplement: Vitamin B12
Dietary Supplement: Folic Acid
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Objective Responses Assessed by International Workshop Criteria (IWC) [ Time Frame: Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I ] [ Designated as safety issue: No ]
    Number of participants who achieved an objective response. Objective response was defined as a tumor response assessment of either complete response (CR) or partial response (PR) and was determined only for patients with measurable disease at baseline. A tumor response assessment reported by IWC without PET was used for any analyses in cases where an IWC+PET evaluation was not done.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study ] [ Designated as safety issue: No ]
    Duration of response was defined as the number of days between the date of first tumor response assessment of objective response to the time of the first tumor response assessment of progressive disease (PD) or death due to any cause (date of first PD assessment or death - date of first objective response assessment + 1)

  • Progression-free Survival (PFS) Time [ Time Frame: Response assessments were performed no less than every 3 cycles in the Phase 1 part of the study and every 8 weeks (± 1 week) in the Phase 2a part of the study ] [ Designated as safety issue: No ]
    PFS time was calculated as the number of days from study day 1 to the date of PD or death, regardless of cause (date of PD or death - study day 1 + 1).


Enrollment: 119
Study Start Date: May 2007
Study Completion Date: August 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pralatrexate & Gemcitabine - Sequential Days 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.

Other Names:
  • FOLOTYN
  • PDX
  • Pralatrexate
  • (RS)-10-propargyl-10-deazaaminopterin
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.

Other Names:
  • Gemcitabine
  • Gemzar®, Eli Lilly and Company
  • Gemcitabine Hydrochloride (HCl) for Injection
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.

Other Name: Cyanocobalamin
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.

Other Names:
  • Vitamin B9
  • Folate
  • Folacin
Experimental: Pralatrexate & Gemcitabine - Same Day 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.

Other Names:
  • FOLOTYN
  • PDX
  • Pralatrexate
  • (RS)-10-propargyl-10-deazaaminopterin
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.

Other Names:
  • Gemcitabine
  • Gemzar®, Eli Lilly and Company
  • Gemcitabine Hydrochloride (HCl) for Injection
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.

Other Name: Cyanocobalamin
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.

Other Names:
  • Vitamin B9
  • Folate
  • Folacin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00481871

Locations
United States, California
University of California at Los Angeles
Los Angeles, California, United States, 90095-7077
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Illinois
University of Chicago Hospital
Chicago, Illinois, United States, 60637
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115-6013
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
New York University Hospital
New York, New York, United States, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10017
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Cancer Therapy & Research Center
San Antonio, Texas, United States, 78229-4427
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Michael Saunders, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT00481871     History of Changes
Other Study ID Numbers: PDX-009
Study First Received: June 1, 2007
Results First Received: August 20, 2012
Last Updated: May 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Lymphoproliferative malignancies
Lymphoma
Hodgkin's lymphoma (HL)
Non-Hodgkin's lymphoma (NHL)
PTCL
T/NK-cell leukemia/lymphoma
T-cell lymphoma/leukemia (HTLV 1+)
Angioimmunoblastic T-cell lymphoma
Blastic NK lymphoma
Anaplastic large cell lymphoma
T/NK-cell lymphoma
Enteropathy-type intestinal lymphoma
Hepatosplenic T-cell lymphoma
Extranodal peripheral T/NK-cell lymphoma
Subcutaneous panniculitis T-cell lymphoma
Transformed mycosis fungoides
PDX
Pralatrexate
Gemcitabine
Gemzar
Vitamin B12
Folic acid

Additional relevant MeSH terms:
Neoplasms
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, T-Cell
Lymphoma
Waldenstrom Macroglobulinemia
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Vitamins
Vitamin B 12
Hydroxocobalamin
Folic Acid
Gemcitabine
10-deazaaminopterin
Aminopterin
Vitamin B Complex
Micronutrients

ClinicalTrials.gov processed this record on October 01, 2014