Clinical trial NCT00481871: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Lymphoproliferative Malignancies
Hodgkin's Lymphoma
Peripheral T-cell Lymphoma
B-cell Lymphoma
Waldenstrom's Macroglobulinemia
Keywords: 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
Lead sponsor: Acrotech Biopharma Inc.
Sponsor class: INDUSTRY
First posted: 2007-06-04
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Objective Responses Assessed by International Workshop Criteria (IWC)
timeFrame: Assessed every 8 weeks (+/- 1 week) for Phase II and no less than every 3 cycles for Phase I
Secondary outcomes:
measure: Duration of Response
timeFrame: 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
measure: Progression-free Survival (PFS) Time
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Chicago
country: United States
facility: University of Chicago Hospital
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: The Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Spectrum Pharmaceuticals, Inc
name: Michael Saunders, MD
role: STUDY_DIRECTOR
References: