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

Peripheral T-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00481871
• Other study ID #: PDX-009
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2007
• Est. completion date: August 2011

Study information

• Verified date: December 2019
• Source: Acrotech Biopharma LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: August 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Lymphoma
• Hodgkin Disease
• Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Neoplasms
• Peripheral T-cell Lymphoma
• Relapsed or Refractory Lymphoproliferative Malignancies
• Waldenstrom Macroglobulinemia
• Waldenstrom's Macroglobulinemia

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago Hospital	Chicago	Illinois
United States	Rocky Mountain Cancer Center	Denver	Colorado
United States	The Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	University of California at Los Angeles	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York University Hospital	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Cancer Therapy & Research Center	San Antonio	Texas
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Acrotech Biopharma LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Responses Assessed by International Workshop Criteria (IWC)	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.	Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I
Secondary	Duration of Response	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)	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
Secondary	Progression-free Survival (PFS) Time	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).	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