Combination fludarabine and cyclophosphamide (FC) plus Ofatumumab at Standard or Mega dose In Chronic lymphoid leukemia (CLL)
| ISRCTN | ISRCTN51382468 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51382468 |
| EudraCT/CTIS number | 2011-000796-14 |
| Secondary identifying numbers | HM10/9652 |
- Submission date
- 29/07/2011
- Registration date
- 21/09/2011
- Last edited
- 15/12/2021
- 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
Prof Peter Hillmen
Scientific
Scientific
Department of Haematology
Bexley Wing
St James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
| Phone | +44 (0)113 206 8513 |
|---|---|
| peter.hillmen@nhs.net |
Study information
| Study design | Phase II multi-centre randomised open parallel group trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| 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 | Combination fludarabine and cyclophosphamide (FC) plus Ofatumumab at Standard or Mega dose In Chronic lymphoid leukemia (CLL): a phase II, multi-centre, randomised, open, parallel group trial |
| Study acronym | COSMIC |
| Study objectives | This trial will assess the efficacy of standard dose and high (mega) dose of ofatumumab in combination with chemotherapy (fludarabine and cyclophosphamide) in relapsed B-CLL patients. |
| Ethics approval(s) | Research Ethics Committee: Yorkshire & The Humber – Leeds East, 24/10/2011, ref: 11/YH/0260 |
| Health condition(s) or problem(s) studied | Chronic Lymphocytic Leukaemia (CLL) |
| Intervention | 1. Fludarabine, cyclophosphamide and standard dose ffatumumab (Standard Of-FC): 1.1. Fludarabine (oral*) - 24mg/m2/day - Day 1 to 5 (Cycle 1 to 6) 1.2. Cyclophosphamide (oral*) - 150mg/m2/day - Day 1 to 5 (Cycle 1 to 6) 1.3. Ofatumumab [intravenous (IV)] - 300mg - Day 1 and 1000mg Day 8 (Cycle 1 only) 1.4. Ofatumumab (IV) - 1000mg - Day 1 (Cycle 2 to 6) 2. Fludarabine, cyclophosphamide and high dose ofatumumab (Mega-Of-FC): 2.1. Fludarabine (oral*) - 24mg/m2/day - Day 1 to 5 (Cycle 1 to 6) 2.2. Cyclophosphamide (oral*) - 150mg/m2/day - Day 1 to 5 (Cycle 1 to 6) 2.3. Ofatumumab (IV) - 300mg - Day 1 (Cycle 1) followed by 2000mg weekly for 8 doses, followed by 2000mg monthly for 3 doses |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Fludarabine, cyclophosphamide, ofatumumab |
| Primary outcome measure | Proportion of patients achieving a Complete Response (CR or CR(i)), as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. Measured 3 months after the therapy. |
| Secondary outcome measures | 1. Proportion of patients with undetectable minimal residual disease (MRD) 2. Overall response rate defined as complete or partial remission by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria 3. Progression-free survival at 2 years 4. Overall survival at 2 years 5. Time to MRD relapse in MRD negative patients 6. Safety and toxicity |
| Overall study start date | 01/01/2012 |
| Completion date | 01/07/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 82 |
| Total final enrolment | 62 |
| Key inclusion criteria | 1. At least 18 years old 2. Chronic lymphocytic leukaemia requiring therapy 3. Previous treatment with at least one chemotherapeutic regime 4. Be capable of giving written informed consent 5. World Health Organisation (WHO) performance status (PS) of 0, 1, or 2 6. Life expectancy of at least 12 weeks 7. Considered fit enough to receive fludarabine-based combinations |
| Key exclusion criteria | 1. Fludarabine refractory: defined as no response to or relapse within 6 months of fludarabine alone or in combination with cyclophosphamide (FC) 2. Relapse within 12 months of FC with rituximab (FCR) 3. Deletion of chromosome 17p on fluorescent in-situ hybridisation (FISH) [will be performed in Haematological Malignancy Diagnostic Service (HMDS) at screening] 4. Previous treatment with ofatumumab either alone or in combination with chemotherapy 5. Toxicity attributable to purine analogues such as autoimmune haemolytic anaemia, neurological toxicity or allergy 6. Active infection 7. Other severe, concurrent (particularly cardiac or pulmonary) diseases or mental disorders that could interfere with their ability to participate in the study 8. Patients with a creatinine clearance of less than 30ml/min (either measured or derived by the Cockcroft-Gault formula) 9. Pregnant, lactating or women of child bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished 10. Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished, unless they are surgically sterile 11. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per Investigator assessment) 12. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrolment, whichever is longer, or currently participating in any other interventional clinical study 13. Other past or current malignancy. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. 14. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy 15. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C 16. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae 17. Known human immunodeficiency (HIV) positive 18. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomisation, congestive heart failure New York Heart Association (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. 19. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the Investigator may represent a risk for the patient. 20. 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 21. Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result screening laboratory values: 21.1. Platelets <50 x 109/L (unless due to involvement by CLL) 21.2. Neutrophils <1.0 x 109/L (unless due to involvement by CLL) 21.3. Creatinine clearance below 30ml/min (between 30 and 60ml/min the fludarabine dose will be reduced) 21.4. Total bilirubin >1.5 times upper normal limit (unless due to CLL involvement of liver or a known history of Gilberts disease) 21.5. Alanine aminotransferase (ALT) >2.5 times upper normal limit (unless due to CLL involvement of liver) 21.6. Alkaline phosphatase >2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow by CLL) |
| Date of first enrolment | 01/01/2012 |
| Date of final enrolment | 01/07/2013 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
St James's University Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
Sponsor information
Leeds Teaching Hospitals NHS Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Research and Development
34 Hyde Terrace
Leeds
LS9 6LN
England
United Kingdom
| Phone | +44 (0)113 392 2878 |
|---|---|
| derek.norfolk@leedsth.nhs.uk | |
"ROR" |
https://ror.org/00v4dac24 |
Funders
Funder type
Industry
GlaxoSmithKline
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 | 01/07/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | The results will be published in July 2018. |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 20/09/2016 | Yes | No | |
| Results article | 01/08/2021 | 04/06/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/06/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
26/06/2017: Publication and dissemination plan added.
21/09/2016: Publication reference added.
