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

This study is currently recruiting participants.
Verified January 2012 by University of Oxford
Sponsor:
Collaborators:
GlaxoSmithKline
Cancer Research UK
Oxford University Hospitals NHS Trust
NCRI CLL Subgroup
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01171378
First received: July 22, 2010
Last updated: January 6, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Richter's Syndrome
Drug: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Objective response [ Time Frame: Week 20 ] [ Designated as safety issue: No ]

    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:
  • Overall survival [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 35
Study Start Date: April 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Ofatumumab
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Computerised 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:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01171378

Contacts
Contact: Anna Schuh, MD, PhD, MRCP, FRCPath 01865 225329 anna.schuh@ndcls.ox.ac.uk
Contact: Anne Francis, DPhil 01865 617088 chop-or@octo-oxford.org.uk

Locations
United Kingdom
Queen Elizabeth Hospital Birmingham Recruiting
Birmingham, United Kingdom, B15 2TT
Principal Investigator: Jim Murray         
Sub-Investigator: Paul Moss         
Royal Bournemouth Hospital Recruiting
Bournemouth, United Kingdom, BH7 7DW
Principal Investigator: David Oscier         
Sub-Investigator: Joseph Chacko         
Sub-Investigator: Rachel Hall         
Sub-Investigator: Helen McCarthy         
Sub-Investigator: Renata Walewska         
Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom, CB2 0QQ
Principal Investigator: George Follows         
St James University Hospital Recruiting
Leeds, United Kingdom, LS9 7TF
Principal Investigator: Peter Hillmen         
Sub-Investigator: Anne Critchley         
Sub-Investigator: Anita Hill         
Sub-Investigator: Rod Johnson         
Sub-Investigator: Roger Owen         
Royal Liverpool University Hospital Recruiting
Liverpool, United Kingdom, L7 8XP
Principal Investigator: Andrew Pettitt         
Sub-Investigator: Nagesh Kalakonda         
St Bartholomew's Hospital Recruiting
London, United Kingdom, EC1A 7BE
Principal Investigator: John Gribben         
Sub-Investigator: Samir Agwaral         
Kings College Hospital Recruiting
London, United Kingdom, SE5 9RS
Principal Investigator: Stephen Devereux         
Christie Hospital Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Adrian Bloor         
Churchill Hospital Recruiting
Oxford, United Kingdom, OX3 7LJ
Principal Investigator: Anna Schuh, MD, PhD, MRCP, FRCPath         
Sub-Investigator: Graham Collins         
Sub-Investigator: Chris Hatton         
Sponsors and Collaborators
University of Oxford
GlaxoSmithKline
Cancer Research UK
Oxford University Hospitals NHS Trust
NCRI CLL Subgroup
Investigators
Principal Investigator: Anna Schuh, MD, PhD, MRCP, FRCPath Oxford University Hospitals NHS Trust
  More Information

Additional Information:
No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01171378     History of Changes
Other Study ID Numbers: OCTO_018, OFT113560, 2009-016459-23
Study First Received: July 22, 2010
Last Updated: January 6, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Institute for Health Research
United Kingdom: Research Ethics Committee

Keywords provided by University of Oxford:
Richter's Syndrome
High-grade transformation in patients with B cell chronic lymphocytic leukemia
Feasibility
Ofatumumab Induction and maintenance
CHOP
CHOP-0
CHOP-OR
Non Hodgkin's lymphoma

ClinicalTrials.gov processed this record on April 23, 2014