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
| ISRCTN | ISRCTN88860946 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN88860946 |
| EudraCT/CTIS number | 2009-016459-23 |
| ClinicalTrials.gov number | NCT01171378 |
| Secondary identifying numbers | 9476 |
- Submission date
- 30/03/2011
- Registration date
- 30/03/2011
- Last edited
- 26/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr Lucinda Boyle
Scientific
Scientific
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
Study information
| Study design | Non-randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| 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 |
| Study acronym | CHOP-OR |
| Study objectives | 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(s) | 10/H0604/85; First MREC approval date 05/11/2010 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 30/04/2011 |
| Completion date | 31/05/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 35; UK Sample Size: 35 |
| Total final enrolment | 37 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 30/04/2011 |
| Date of final enrolment | 31/05/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Oxford
Oxford
OX3 7DQ
United Kingdom
OX3 7DQ
United Kingdom
Sponsor information
University of Oxford
University/education
University/education
Clinical Trial & Research Governance Team
Joint Research Office
Block 60
Churchill Hospital
Old Road
Oxford
OX3 7LE
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Industry
GlaxoSmithKline (UK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Protocol article | protocol | 13/02/2015 | Yes | No | |
| Results article | results | 01/10/2016 | 25/04/2019 | Yes | No |
| Plain English results | 26/10/2022 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
25/10/2022: Cancer Research UK plain English results link added.
25/04/2019: Added EudraCT link to basic results (scientific). Publication reference and total final enrolment added.
02/02/2017: Publication reference added.
14/03/2014: The overall trial end date was changed from 30/04/2013 to 31/05/2014.
25/01/2013: The following changes were made to the trial record:
1. The overall trial start date was changed from 31/01/2011 to 30/04/2011.
2. The overall trial end date was changed from 31/01/2013 to 30/04/2013.
