Clinical Trial: Study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) With Ofatumumab in Patients With Richter's Syndrome

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

Official Title: Single Arm NCRI Feasibility Study of CHOP in Combination With Ofatumumab in Induction and Maintenance for Patients With Newly Diagnosed Richter's Syndrome

Brief Summary: The purpose of this study is to evaluate Ofatumumab in combination with CHOP (cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone, the standard chemotherapy treatment) in induction and maintenance treatment of Richter's Syndrome. This study aims to evaluate the overall response rate to CHOP-O (CHOP in combination with Ofatumumab) according to the Revised Response Criteria for Malignant Lymphoma. The hypothesis would be that treatment with CHOP-O for Richter's Syndrome (RS), shows a difference in overall survival (more people living longer), when compared with the standard treatment of CHOP-R (CHOP chemotherapy plus Rituximab).

Detailed Summary:

Richter's Syndrome (RS) is a high-grade transformation that occurs in 5-15% of patients with B cell chronic lymphocytic leukaemia (B-CLL). RS is a complication of B-CLL in which the leukemia changes into a fast-growing diffuse large B cell lymphoma (DLBCL). The pathogenesis (mechanism by which the disease is caused) of RS is poorly understood and predictors of transformation and response to treatment are unknown. Management of RS remains unsatisfactory; the mean overall survival of patients treated with conventional chemo-immunotherapy such as CHOP-R is 8 months from the end of treatment.

CHOP is the acronym for a chemotherapy regimen, cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone) and the R stands for the monoclonal antibody, Rituximab. Ofatumumab, a next generation monoclonal anti CD20 antibody, has proven single agent activity in relapsed/refractory B-CLL and other non-Hodgkin lymphomas. In addition, it has shown a favourable safety profile in the maintenance setting.

Therefore, we propose to evaluate Ofatumumab in combination with CHOP in induction and maintenance treatment of patients with RS.

The primary objective of the study will be to evaluate overall response rate (ORR) to CHOP-O (CHOP chemotherapy plus Ofatumumab) according to the Revised Response Criteria for Malignant Lymphoma (Cheson).

Secondary objectives will be feasibility of recruitment, progression free survival and overall survival, the clinical benefit and changes in patient reported outcome measures, safety and tolerability.

This is a multi-centre non-randomised Phase II National Cancer Research Institute (NCRI) feasibility study in 35 patients wi
Sponsor: University of Oxford

Current Primary Outcome: Objective response [ Time Frame: Week 20 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Overall survival [ Time Frame: 72 weeks ]
  Overall survival where length of survival is defined in whole days as the time from entry into the study until death from any cause. For those who are not observed to die during the course of the trial will be censored at their last known follow-up date.
• Progression free survival [ Time Frame: 72 weeks ]
  Progression free survival where length of survival is defined in whole days as the time from entry into the study until lymphoma progression or death from any cause. For those who are not observed to progress or die during the course of the trial will be censored at their last known progression-free follow-up date
• Duration of response [ Time Frame: 72 weeks ]
  Duration of response defined in whole days as the time between recorded response to disease progression or death from any cause. Patients will be censored at the date of their last follow-up visit at which the response was assessed.
• Time to next DLBCL therapy [ Time Frame: 72 weeks ]
  Time to next DLBCL therapy defined in whole days as the time from the end of study treatment and the start of the next DLBCL therapy other than CHOP in combination with ofatumumab. Patients will be censored at the date of their last follow-up visit at which the further treatment was assessed.
• Reduction in Tumour Size [ Time Frame: 13, 20 and 72 weeks ]
  Reduction in Tumour Size will be measured by the absolute value of and percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from screening to post-baseline computerised tomography (CT) scans. CT scans will be complemented by positron emission tomography (PET) scanning in patients with bulky (>5cm) lymphadenopathy from B-CLL.
• Patient reported outcomes [ Time Frame: Baseline, week 13, week 20, every 2 months until week 72 and at week 72. ]
  Patient reported outcomes these will be assessed using the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionaire) and the EORTC QLQ-CLL16 at baseline and regular follow-up visits throughout the trial.
• Safety [ Time Frame: Throughout trial and up to 4 weeks post end of treatment ]
  Safety - Adverse events (AE) and abnormal clinical and laboratory findings will be collected at all follow-up visits and up to 4 weeks post end of treatment.

Original Secondary Outcome: Same as current

Information By: University of Oxford

Dates:
Date Received: July 22, 2010
Date Started: April 2011
Date Completion: April 2016
Last Updated: May 27, 2015
Last Verified: May 2015