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

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Brief Title

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

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 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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Objective response

Secondary Outcome

 Overall survival

Condition

Richter's Syndrome

Intervention

Ofatumumab

Study Arms / Comparison Groups

 Ofatumumab
Description:  Single arm study

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

43

Start Date

April 2011

Completion Date

April 19, 2016

Primary Completion Date

February 2015

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Anna Schuh, MD, PhD, MRCP, FRCPath, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT01171378

Organization ID

OCTO_018

Secondary IDs

OFT113560

Responsible Party

Sponsor

Study Sponsor

University of Oxford

Collaborators

 GlaxoSmithKline

Study Sponsor

Anna Schuh, MD, PhD, MRCP, FRCPath, Principal Investigator, Oxford University Hospitals NHS Trust


Verification Date

April 2018