Condition category
Cancer
Date applied
30/03/2011
Date assigned
30/03/2011
Last edited
14/03/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Lucinda Boyle

ORCID ID

Contact details

Oncology Clinical Trials Office (OCTO)
Department of Oncology
Old Road Campus Research Building
University of Oxford
Old Road Campus
Off Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom

Additional identifiers

EudraCT number

2009-016459-23

ClinicalTrials.gov number

NCT01171378

Protocol/serial number

9476

Study information

Scientific title

Acronym

CHOP-OR

Study hypothesis

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 NCRI feasibility study in 35 patients with newly diagnosed RS 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.
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. The pathogenesis 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.

On 25/01/2013 the following changes were made to the trial record:
1. The anticipated start date was updated from 31/01/2011 to 30/04/2011
2. The anticipated end date was updated ffrom 31/01/2013 to 30/04/2013

On 14/03/2014 the anticipated end date was changed from 30/04/2013 to 31/05/2014.

Ethics approval

10/H0604/85; First MREC approval date 05/11/2010

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Haematological Oncology, Lymphoma; Disease: Leukaemia (chronic), Lymphoma (non-Hodgkin's)

Intervention

CHOP-O (CHOP with Ofatumumab), Subjects will be given CHOP in combination with ofatumumab (CHOP-O).
CHOP-O is CHOP (cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and prednisone/prednisolone) in combination with the monoclonal antibody, ofatumumab.
The first 4 infusions of CHOP will be weekly. CHOP-O will be given every 3 weeks for six cycles during induction. Subjects will then receive ofatumumab maintenance treatment once every eight weeks for 6 cycles.; Follow Up Length: 3 month(s); Study Entry : Registration only

Intervention type

Drug

Phase

Phase II

Drug names

Cyclophosphamide
Hydroxydaunorubicin
Oncovin
Prednisone
Ofatumumab

Primary outcome measures

Objective response; Timepoint(s): Objective response as defined by the revised response criteria for malignant lymphoma.

Secondary outcome measures

1. To assess feasibility of recruitment
2. To further assess the efficacy of CHOP in combination with ofatumumab in induction and maintenance treatment of Richter‘s Syndrome
3. To assess the safety and tolerability of CHOP in combination with ofatumumab in induction and maintenance treatment of Richter‘s Syndrome

Overall trial start date

30/04/2011

Overall trial end date

31/05/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 14/03/2014:
1. Signed written informed consent prior to performing any study-specific procedures
2. Patients with B-CLL and newly diagnosed not previously treated and biopsy proven Richter’s transformation - Diffuse large B-cell lymphoma (DLBCL)
3. Computerised tomography (CT) scan performed within 8 weeks prior to starting treatment
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3
5. Age 18 years and over
6. Target gender: male and female
7. Lower age limit 18 years

Previous inclusion criteria:
1. Signed written informed consent prior to performing any study-specific procedures
2. Patients with B-CLL and newly diagnosed not previously treated and biopsy proven Richter’s transformation - Diffuse large B-cell lymphoma (DLBCL)
3. Computerised tomography (CT) scan performed within 6 weeks prior to starting treatment
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3
5. Age 18 years and over
6. Target gender: male and female
7. Lower age limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 35; UK Sample Size: 35

Participant exclusion criteria

Current exclusion criteria as of 14/03/2014:
1. CHOP or CHOP-like antracycline-containing treatment for DLBCL within 6 months prior to registration
2.Known CNS involvement 1. Treatment for Diffuse large B-cell lymphoma (DLBCL) within 6 months prior to registration
2. Known CNS involvement of B-cell chronic lymphocytic leukemia (B-CLL)
3. Any other malignancy that requires active treatment with the exception of basal cell carcinoma and non-invasive squamous cell carcinoma
4. Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to:
4.1. Chronic renal infection
4.2. Chronic chest infection with bronchiectasis
4.3. Tuberculosis
4.4. Active hepatitis
5. Subjects meeting any of the following criteria must not be enrolled in the study:
5.1. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. (In addition, if negative for HBsAg but HBcAb 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.
5.2. Clinically significant cardiac disease including:
5.2.1. Unstable angina
5.2.2. Uncontrolled congestive heart failure
5.2.3. Arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
5.3. Significant concurrent, uncontrolled medical condition including, but not limited to:
5.3.1. Renal
5.3.2. Hepatic
5.3.3. Haematological
5.3.4. Gastrointestinal
5.3.5. Endocrine
5.3.6. Pulmonary
5.3.7. Neurological
5.3.8. Cerebral or psychiatric disease
5.4. History of significant cerebrovascular disease in last 6 months
5.5. Known HIV positive
6. Known or suspected hypersensitivity to components of investigational product
7. 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)
8. Current participation in any other interventional clinical study
9. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
10. Breast feeding women or women with a positive pregnancy test at screening.
11. 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

Previous exclusion criteria:
1.Treatment for DLBCL within 6 months prior to registration
2.Known CNS involvement 1. Treatment for Diffuse large B-cell lymphoma (DLBCL) within 6 months prior to registration
2. Known CNS involvement of B-cell chronic lymphocytic leukemia (B-CLL)
3. Any other malignancy that requires active treatment with the exception of basal cell carcinoma and non-invasive squamous cell carcinoma
4. Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to:
4.1. Chronic renal infection
4.2. Chronic chest infection with bronchiectasis
4.3. Tuberculosis
4.4. Active hepatitis
5. Subjects meeting any of the following criteria must not be enrolled in the study:
5.1. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. (In addition, if negative for HBsAg but HBcAb 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.
5.2. Clinically significant cardiac disease including:
5.2.1. Unstable angina
5.2.2. Congestive heart failure
5.2.3. Arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
5.3. Significant concurrent, uncontrolled medical condition including, but not limited to:
5.3.1. Renal
5.3.2. Hepatic
5.3.3. Haematological
5.3.4. Gastrointestinal
5.3.5. Endocrine
5.3.6. Pulmonary
5.3.7. Neurological
5.3.8. Cerebral or psychiatric disease
5.4. History of significant cerebrovascular disease in last 6 months
5.5. Known HIV positive
6. Known or suspected hypersensitivity to components of investigational product
7. 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)
8. Current participation in any other interventional clinical study
9. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
10. Breast feeding women or women with a positive pregnancy test at screening.
11. 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

Recruitment start date

30/04/2011

Recruitment end date

31/05/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Oncology Clinical Trials Office (OCTO)
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trial & Research Governance Team
Joint Research Office
Block 60
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

GlaxoSmithKline (UK)

Alternative name(s)

GlaxoSmithKline Plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes