Clinical Trial: A Phase II Study to Evaluate Efficacy and Safety of P276-00 in Relapsed and/or Refractory Mantle Cell Lymphoma

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of P276-00 in Patients With Relapsed and/or Refractory Mantle Cell Lymphoma

Brief Summary: The purpose of this study is to determine whether P276-00 is safe and effective in treatment of Mantle Cell Lymphoma that is recurred after or not responding to at least one previous line of treatment.

Detailed Summary:

Despite response rates of up to 97% with first-line standard or high-intensity chemotherapy, with or without stem-cell transplantation, most patients of mantle cell lymphoma (MCL)relapse.Prognosis of MCL after first relapse is very poor with median survival of around 1 to 2 years. Therefore, novel therapies are required for relapsed and/or refractory MCL.Overexpression of Cyclin D1 as a result of t(11;14)(q13;q32) translocation is the hallmark of MCL.It is postulated that Cyclin D1 may also have an oncogenic role independent of pRb in MCL.Therefore, inhibition of Cdk4-Cyclin D1 is a potentially promising target in MCL. P276-00 is a potent Cdk4-Cyclin D1 inhibitor worth exploring for its efficacy in MCL. Hence, this Phase II study is planned to examine the efficacy and safety of P276-00 in the treatment of patients with relapsed and/or refractory MCL.

This is an open-label, single-arm, 2-stage trial. Approximately 35 patients are planned to be enrolled into the study to obtain a total of 25 efficacy evaluable patients (patients who complete at least 2 cycles of study treatment and have tumor measurements at the end of 2 cycles). A total of 15 efficacy evaluable patients are planned to be treated in Stage I of the study. If ≥1 response (CR or PR) of any duration or ≥2 stable disease (SD) for ≥4 cycles are seen in the Stage I, then the study will continue into Stage II, in which additional patients will be treated until there are 10 additional efficacy evaluable patients.The study is divided into 3 periods: Screening, Treatment, and Follow-up. During the Screening Period, patients will provide written informed consent and be evaluated for inclusion and exclusion criteria. During the Treatment Period, patients will be administered P276-00 as intravenous (iv) infusion on Days 1 to 5 of each 21-day cycle for a minimum of 6 cycles and a maximum of 12 cycles, or
Sponsor: Piramal Enterprises Limited

Current Primary Outcome: Best Overall Objective Response Rate [ Time Frame: End of every 2 cycles and end of the study treatment ]

The primary efficacy endpoint is the proportion of subjects achieving an objective response. The proportion of patients achieving an objective response is the best overall objective response rate.


Original Primary Outcome: Best Overall Objective Response Rate [ Time Frame: End of every 2 cycles and end of the study treatment ]

Current Secondary Outcome:

  • Duration of Response [ Time Frame: End of the study treatment ]
    It is defined as the time from when the measurement criteria are met for complete or partial response until the first date that recurrent or progressive disease is objectively or clinically documented.
  • Time to Progression [ Time Frame: End of study treatment ]
    It is defined as the time from day 1 of the study drug administration until the first date of progressive disease.


Original Secondary Outcome:

  • Duration of Response [ Time Frame: End of the study treatment ]
  • Time to Progression [ Time Frame: End of study treatment ]


Information By: Piramal Enterprises Limited

Dates:
Date Received: February 12, 2009
Date Started: November 2009
Date Completion: August 2012
Last Updated: June 20, 2012
Last Verified: June 2012