Study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) With Ofatumumab in Patients With Richter's Syndrome (CHOP-OR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01171378
Recruitment Status : Unknown
Verified May 2015 by University of Oxford.
Recruitment status was:  Active, not recruiting
First Posted : July 28, 2010
Last Update Posted : May 28, 2015
Cancer Research UK
Oxford University Hospitals NHS Trust
NCRI CLL Subgroup
Information provided by (Responsible Party):
University of Oxford

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).

Condition or disease Intervention/treatment Phase
Richter's Syndrome Drug: Ofatumumab Phase 2

Detailed Description:

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 with newly diagnosed Richter's Syndrome in the UK. CHOP-O will be given for six cycles followed by six cycles of Ofatumumab maintenance treatment every eight weeks and a three months follow-up period. The total duration of recruitment will be 24 months starting from the opening of the first site.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : April 2011
Actual Primary Completion Date : February 2015
Estimated Study Completion Date : April 2016

Arm Intervention/treatment
Single arm study
Drug: Ofatumumab

1000mg vials (50ml @ 20mg/ml), or 100mg vials (5ml @20mg/ml), to be given as an Intravenous (IV) infusion.

Ofatumumab will be infused intravenously on day 1 (300 mg), day 8 (1000 mg) and day 15 (1000mg) in the first cycle, followed by infusions every 3 weeks of 1000 mg on the first day of each cycle for a total of 6 cycles. Maintenance treatment will start 4 weeks after day 1 of cycle 6 in week 20 and consists of six infusions of ofatumumab every 8 weeks

Other Name: Arzerra

Primary Outcome Measures :
  1. Objective response [ Time Frame: Week 20 ]

    Objective response as defined by the revised response criteria for malignant lymphoma (Cheson et al, JCO, Vol 25, No 5, 2007).

    Patients will be classified as responders/non-responders as follows: complete remission (CR), nodular partial remission (nPR) and partial remission (PR) are classified as responders; while stable disease (SD) and progressive disease (PD) are classified as non-responders. Non-evaluable patients will be classified as non-responders.

Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed written informed consent prior to performing any study-specific procedures
  • Patients with B-CLL and newly diagnosed not previously treated and biopsy proven DLBCL Richter's transformation
  • Computerized tomography (CT) scan performed within 6 weeks prior to starting treatment.
  • ECOG (Eastern Cooperative Oncology Group) Performance Status of 0, 1, 2 or 3
  • Age 18 years and over.

Exclusion Criteria:

  • CHOP or CHOP-like anthracycline containing treatment for DLBCL within 6 months prior to registration.
  • Known central nervous system (CNS) involvement of B-CLL.
  • Any malignancy that requires active treatment with the exception of basal cell carcinoma and non-invasive squamous cell carcinoma.
  • Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis.
  • Subjects meeting any of the following criteria must not be enrolled in the study:
  • Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg (the surface antigen of the Hepatitis-B-Virus). In addition, if negative for HBsAg but HBcAb (Hepatitis B core Antibody) positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. Consent will be sought prior to any test being performed.
  • Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.
  • History of significant cerebrovascular disease in last 6 months.
  • Known Human immunodeficiency virus (HIV) positive.
  • Known or suspected hypersensitivity to components of investigational product.
  • Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2 (start of treatment, cycle 1, day 1).
  • Current participation in any other interventional clinical study.
  • Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
  • Breast feeding women or women with a positive pregnancy test at screening.
  • Women of childbearing potential not willing to use adequate contraception during study and for 12 months after last dose of Ofatumumab. Adequate contraception is defined as abstinence, hormonal birth control or intrauterine devices.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01171378

United Kingdom
Queen Elizabeth Hospital Birmingham
Birmingham, United Kingdom, B15 2TT
Royal Bournemouth Hospital
Bournemouth, United Kingdom, BH7 7DW
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
St James University Hospital
Leeds, United Kingdom, LS9 7TF
Royal Liverpool University Hospital
Liverpool, United Kingdom, L7 8XP
St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Kings College Hospital
London, United Kingdom, SE5 9RS
Christie Hospital
Manchester, United Kingdom, M20 4BX
Churchill Hospital
Oxford, United Kingdom, OX3 7LJ
Sponsors and Collaborators
University of Oxford
Cancer Research UK
Oxford University Hospitals NHS Trust
NCRI CLL Subgroup
Principal Investigator: Anna Schuh, MD, PhD, MRCP, FRCPath Oxford University Hospitals NHS Trust

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Oxford Identifier: NCT01171378     History of Changes
Other Study ID Numbers: OCTO_018
OFT113560 ( Other Grant/Funding Number: Funder: GlaxoSmithKline )
2009-016459-23 ( EudraCT Number )
First Posted: July 28, 2010    Key Record Dates
Last Update Posted: May 28, 2015
Last Verified: May 2015

Keywords provided by University of Oxford:
Richter's Syndrome
High-grade transformation in patients with B cell chronic lymphocytic leukemia
Ofatumumab Induction and maintenance
Non Hodgkin's lymphoma

Additional relevant MeSH terms:
Pathologic Processes
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs