Clinical Trial: Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

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-

Brief 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

Detailed Summary:

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.

Pa
Sponsor: University of Nebraska

Current Primary Outcome: CR rate of CEOP and P treatment [ Time Frame: Up to 6 courses ]

Original Primary Outcome:

• Overall response rate (ORR) [ Time Frame: 24 weeks or up to 36 weeks (4 courses or up to 6 courses) ]
  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 (CR) [ Time Frame: 24 weeks or up to 36 weeks (4 courses or up to 6 courses) ]
  Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete course of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals. A CR rate > 50% would be promising if the toxicity profile is acceptable.
• Partial response rate (PR) [ Time Frame: 24 weeks or up to 36 weeks (4 courses or up to 6 courses) ]
  Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete course of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals.

Current Secondary Outcome:

• Overall response rates (complete response rates + partial response rates) [ Time Frame: Up to 6 courses ]
  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.
• EFS [ Time Frame: Time from therapy until relapse, progression, or death from any cause, assessed up to 2 years ]
  Estimated 2-year EFS, as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS.
• OS [ Time Frame: Time from the first chemotherapy administered on trial until death from any cause, assessed up to 2 years ]
  Estimated 2-year OS, as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS.
• Safety and tolerability of the regimen [ Time Frame: Up to 6 courses ]
  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.
• Percent of patients who intended to receive transplant versus those who actually proceeded with transplant [ Time Frame: After up to 34 subjects receive transplant ]
  The percentage of patients who intended to receive transplant will be descriptively summarized using percentages at 95% confidence intervals. Among those who intended to receive a transplant, the percentage that proceeded with a transplant will be summarized along with a 95% confidence interval.
• Ability to collect peripheral blood stem cells [ Time Frame: At the end of 4-6 courses for those that go on to transplant ]
  The percentage of patients for whom we were able to collect peripheral blood stem cells will be descriptively summarized using percentages and 95% confidence intervals.

Original Secondary Outcome:

• Estimated event free survival (EFS) [ Time Frame: 2 years ]
  Event-free survival is defined as time from therapy until relapse, progression, or death from any cause. Estimated 2-year EFS, as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS.
• Overall survival (OS) [ Time Frame: 2 years ]
  Overall survival is defined as time from the first chemotherapy administered on trial until death from any cause. Estimated 2-year OS, as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS.
• Percent of patients who intended to receive transplant versus those who actually proceeded with transplant [ Time Frame: (Average) after up to 34 subjects receive transplant ]
  The percentage of patients who intended to receive transplant will be descriptively summarized using percentages at 95% confidence intervals. Among those who intended to receive a transplant, the percentage that proceeded with a transplant will be summarized along with a 95% confidence interval.
• Incidence of adverse events [ Time Frame: When reported by patients and at days 1&15 physical examinations of each 28 day cycle ]
  Every patient who fulfills all aspects of patient eligibility who receives a partial or complete course of chemotherapy will be evaluable for toxicity. 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 cycle. Serious adverse events will be analyzed similarly.

Dates:
Date Received: March 23, 2011
Date Started: July 2011
Date Completion:
Last Updated: January 20, 2013
Last Verified: January 2013