Additional identifiers
EudraCT number
2009-016459-23
ClinicalTrials.gov number
NCT01171378
Protocol/serial number
9476
Study information
Scientific title
Single arm NCRI feasibility study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) in combination with Ofatumumab in induction and maintenance for patients with newly diagnosed Richters syndrome
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.
Richters 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, the aim of this study is to evaluate Ofatumumab in combination with CHOP in induction and maintenance treatment of patients with RS.
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 study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant 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 measure
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 Richters Syndrome
3. To assess the safety and tolerability of CHOP in combination with ofatumumab in induction and maintenance treatment of Richters Syndrome
Overall trial start date
30/04/2011
Overall trial end date
31/05/2014
Reason abandoned (if study stopped)
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 Richters 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 Richters 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
University of Oxford
Oxford
OX3 7DQ
United Kingdom
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
Basic results (scientific)
Publication list
2015 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/25775024