Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma
Condition: Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy
Intervention: prednisone; cyclophosphamide; etoposide; Vincristine; pralatrexate; laboratory biomarker analysis; comparative genomic hybridization; gene expression analysis; nucleic acid sequencing; mutation analysis; immunohistochemistry staining method; microarray analysis; RNA analysis
Intervention description: Given PO; Given IV; Given PO or IV; Given IV; Given IV; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies; Correlative studies
Intervention MeSH terms: Prednisone; Cyclophosphamide; Etoposide; Vincristine; Etoposide phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well combination chemotherapy and pralatrexate works in
      treating patients with non-Hodgkin lymphoma (NHL). Drugs used in chemotherapy work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed new diagnosis of Stage II, III and IV peripheral T-cell NHL
             not otherwise specified (NOS), anaplastic large cell lymphoma (ALK negative) (ALK
             positive if international prognostic index [IPI] 3, 4, or 5), angioimmunoblastic
             T-cell lymphoma, enteropathy associated T-cell lymphoma, hepatosplenic gamma delta
             T-cell lymphoma

          -  Pathology material (hematoxylin and eosin [H&E] stain, immunohistochemistry [IHC] and
             pathology report from initial diagnosis, if slides are not available, then 8 unstained
             slides of 4 micron thickness or a representative block should be sent) will be
             reviewed, and the diagnosis confirmed by University Nebraska Medical Center (UNMC)
             pathology department (retrospective diagnostic review: treatment may commence prior to
             the UNMC review)

          -  No prior therapy with the exception of prior radiation therapy and 1 cycle of
             chemotherapy based on current diagnosis and clinical condition

          -  Age 19 years or older (the age of consent in Nebraska); age 18 years or older
             (applicable to states where the age of majority is 18)

          -  Expected survival duration of >= six months

          -  Karnofsky Performance Status >= 70

          -  Absolute neutrophil count (ANC) >= 1000 cells/mm^3, unless due to lymphoma involvement
             of the bone marrow

          -  Platelet Count >= 100 mm^3, unless due to lymphoma involvement of the bone marrow

          -  Total bilirubin =< 1.5 x upper normal limit (ULN), or =< 3 x ULN if documented hepatic
             involvement with lymphoma, or =< 5 x ULN if history of Gilbert's Disease

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5
             x ULN if documented hepatic involvement with lymphoma)

          -  Serum potassium within normal range

          -  Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min

          -  Prothrombin time (PT) or international normalized ratio (INR), and partial
             thromboplastin time (PTT) =< 1.5 x ULN unless patient is receiving anticoagulants; if
             patient is on anticoagulation therapy, levels should be within therapeutic range

          -  Patients with measurable disease; patients with non-measurable but evaluable disease
             may be eligible after discussion with the principal investigator (PI); baseline
             measurements and evaluations must be obtained within 6 weeks of registration to the
             study; abnormal positron emission tomography (PET) scans will not constitute evaluable
             disease, unless verified by computed tomography (CT) scan or other appropriate imaging

          -  Patients with measurable disease must have at least one objective measurable disease
             parameter; a clearly defined, bidimensionally measurable defect or mass measuring at
             least 2 cm in diameter on a CT scan will constitute measurable disease; proof of
             lymphoma in the liver is required by a confirmation biopsy

          -  Women must not be pregnant or breast-feeding due to teratogenic effects of
             chemotherapy

               -  All females of childbearing potential must have a blood test within 2 weeks prior
                  to registration to rule out pregnancy

               -  Pregnancy testing is not required for post-menopausal or surgically sterilized
                  women

          -  Male and female patients of reproductive potential must agree follow accepted birth
             control measures

          -  Patient must be able to adhere to the study visit schedule and other protocol
             requirements

          -  Patients must be willing to give written informed consent, and sign an institutionally
             approved consent form before performance of any study-related procedure not part of
             normal medical care; with the exception of 1 cycle of chemotherapy based on current
             diagnosis and clinical condition, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care

          -  No serious disease or condition that, in the opinion of the investigator, would
             compromise the patient's ability to participate in the study

        Exclusion Criteria:

          -  Pregnant or breast feeding females

          -  Known positive for human immunodeficiency virus (HIV), human T-lymphotropic virus type
             1 (HTLV-1), or infectious hepatitis, type A, B or C or active hepatitis

          -  Major surgery within 2 weeks of study drug administration

          -  Prior malignancies within the past 3 years with exception of adequately treated basal
             cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or
             breast; prostate cancer of Gleason Grade 6 or less with stable prostate-specific
             antigen (PSA) levels

          -  Patients with a diagnosis of other peripheral T-cell lymphoma (PTCL) histologies other
             than those specified in the inclusion criteria

          -  Contraindication to any of the required concomitant drugs or supportive treatments,
             including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
             drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

          -  Any other clinically significant medical disease or condition laboratory abnormality
             or psychiatric illness that, in the Investigator's opinion, may interfere with
             protocol adherence or a subject's ability to give informed consent

          -  Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and
             trimethoprim/sulfamethoxazole will not be allowed, since these may result in delayed
             clearance of pralatrexate