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
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 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 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 Complete Response (CR) or Partial Response (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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
Mayo Clinic, Arizona
Scottsdale, Arizona, United States
Stanford University
Stanford, California, United States
Emory University School Of Medicine
Atlanta, Georgia, United States
University of Chicago
Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment
Complete Response Rate (CR) was reported at the end of the CEOP-P (6 courses for patients not receiving transplant and 4-6 courses for patients receiving transplant). Response assessment was performed by computerized tomography (CT) or positron emission tomography (PET)/CT based on the investigator's preference after cycles 2, 4 and 6. Response was assessed by the treating physician according to the Cheson Revised response criteria (Cheson et al,, 2007) or International Harmonization Project criteria (Cheson, 2007), based on imaging modality used. Complete Response Definition: Disappearance of all evidence of disease Nodal Masses: (a) \[18F\]fluorodeoxyglucose(FDG)-avid or PET positive prior to therapy; mass of any size permitted if PETnegative (b) Variably FDG-avid or PET negative; regression to normal size on CT Spleen, Liver: Not palpable, nodules disappeared Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative
Time frame: 168 days - 252 days (4-6 courses; 42 days per course)
Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR))
Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete courses of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals. Complete Response Definition: Defined in Primary Objective Partial Response Definition: Regression of measurable disease and no new sites, Nodal Masses: \> 50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes 1. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site 2. Variably FDG-avid or PET negative; regression on CT Spleen, Liver:\> 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified
Time frame: 2 years
Event Free Survival (EFS)
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NONE
Enrollment
34
Given IV
Given IV
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Correlative studies
Chicago, Illinois, United States
University of Massachusetts Medical School
Worcester, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Siteman Cancer Center, Washington University
St Louis, Missouri, United States
Eppley Cancer Center, University of Nebraska Medical Center
Omaha, Nebraska, United States
Duke University Medical Center
Durham, North Carolina, United States
Estimated 2-year Event Free Survival (EFS), as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS. Event-free survival is defined as time from therapy until relapse, progression, or death from any cause.
Time frame: 2 years
Overall Survival (OS)
Estimated 2-year Overall Survival (OS), as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS. Overall survival is defined as time from the first chemotherapy administered on trial until death from any cause.
Time frame: 2 years
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events
Adverse events will be summarized using patient level incidence rates so that a patient contributes once to any adverse event. The number and percentage of patients with any adverse event will be summarized for each course. Serious adverse events will be analyzed similarly.
Time frame: 22 months
Percent of Patients Who Proceeded With Transplant
Percentage of patients who received consolidation with high dose therapy and autologous stem cell rescue (HDT/SCR).
Time frame: 168-252 days (4 courses up to 6 courses of treatment)