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

Phase 2
18 Years
Open (Enrolling)
Richter's Syndrome

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Trial Information

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

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.

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

- Computerised tomography (CT) scan performed within 6 weeks prior to starting

- ECOG (Eastern Cooperative Oncology Group) Performance Status of 0, 1, 2 or 3

- Age 18 years and over.

Exclusion Criteria:

- 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, 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response

Outcome Description:

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.

Outcome Time Frame:

Week 20

Safety Issue:


Principal Investigator

Anna Schuh, MD, PhD, MRCP, FRCPath

Investigator Role:

Principal Investigator

Investigator Affiliation:

Oxford University Hospitals NHS Trust


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

April 2011

Completion Date:

September 2014

Related Keywords:

  • Richter's Syndrome
  • Richter's Syndrome
  • High-grade transformation in patients with B cell chronic lymphocytic leukemia
  • Feasibility
  • Ofatumumab Induction and maintenance
  • CHOP
  • CHOP-0
  • Non Hodgkin's lymphoma