Overview

This trial is active, not recruiting.

Conditions anaplastic large cell lymphoma, angioimmunoblastic t-cell lymphoma, hepatosplenic t-cell lymphoma, peripheral t-cell lymphoma
Treatments prednisone, cyclophosphamide, etoposide, vincristine sulfate, pralatrexate, laboratory biomarker analysis, comparative genomic hybridization, gene expression analysis, nucleic acid sequencing, mutation analysis, immunohistochemistry staining method, microarray analysis, rna analysis
Phase phase 2
Sponsor University of Nebraska
Collaborator National Cancer Institute (NCI)
Start date July 2011
End date December 2015
Trial size 34 participants
Trial identifier NCT01336933, 569-10, NCI-2011-00254, P30CA036727

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.
prednisone DeCortin
Given PO
cyclophosphamide CPM
Given IV
etoposide EPEG
Given PO or IV
vincristine sulfate leurocristine sulfate
Given IV
pralatrexate FOLOTYN
Given IV
laboratory biomarker analysis
Correlative studies
comparative genomic hybridization comparative genomic analysis
Correlative studies
gene expression analysis
Correlative studies
nucleic acid sequencing Gene Sequencing
Correlative studies
mutation analysis
Correlative studies
immunohistochemistry staining method immunohistochemistry
Correlative studies
microarray analysis gene expression profiling
Correlative studies
rna analysis
Correlative studies

Primary Outcomes

Measure
CR rate of CEOP and P treatment
time frame: Up to 6 courses

Secondary Outcomes

Measure
Overall response rates (complete response rates + partial response rates)
time frame: Up to 6 courses
EFS
time frame: Time from therapy until relapse, progression, or death from any cause, assessed up to 2 years
OS
time frame: Time from the first chemotherapy administered on trial until death from any cause, assessed up to 2 years
Safety and tolerability of the regimen
time frame: Up to 6 courses
Percent of patients who intended to receive transplant versus those who actually proceeded with transplant
time frame: After up to 34 subjects receive transplant
Ability to collect peripheral blood stem cells
time frame: At the end of 4-6 courses for those that go on to transplant

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase II Study of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) Alternating With Pralatrexate (P) as Front Line Therapy for Patients With Stage II, III and IV Peripheral T-Cell Non-Hodgkin Lymphoma
Principal investigator Julie Vose
Description PRIMARY OBJECTIVES: I. To evaluate in a Phase II study a preliminary estimate of the complete response (CR) rate of a new chemotherapy regimen involving Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) alternating with Pralatrexate (P) as front line therapy for patients with Stage II, III and IV Peripheral T-Cell NHL not otherwise specified (NOS), Anaplastic large cell lymphoma (ALK negative), Angioimmunoblastic T-cell lymphoma, Enteropathy associated T-cell lymphoma, Hepatosplenic gamma delta T-cell lymphoma followed by an optional stem cell transplant with high dose chemotherapy and Autologous stem cell transplant. SECONDARY OBJECTIVES: I. To evaluate partial response (PR). II. To evaluate overall response (CR+PR). III. To evaluate the safety and tolerability of the regimen. IV. To assess the 2 year event free survival (EFS) and overall survival (OS) using this regimen. V. To assess the percentage of patients who intended to receive transplant versus those who actually proceeded with transplant. VI. To evaluate the ability to collect peripheral blood stem cells after this regimen. OUTLINE: Patients receive cyclophosphamide intravenously (IV) and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or orally (PO) once daily (QD) on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. After completion of study treatment, patients are followed up for 2 years (transplant patients) or periodically.
Trial information was received from ClinicalTrials.gov and was last updated in January 2013.
Information provided to ClinicalTrials.gov by University of Nebraska.