Combination fludarabine and cyclophosphamide (FC) plus Ofatumumab at Standard or Mega dose In Chronic lymphoid leukemia (CLL)
- Conditions
- Chronic Lymphocytic Leukaemia (CLL)Cancer
- Registration Number
- ISRCTN51382468
- Lead Sponsor
- eeds Teaching Hospitals NHS Trust (UK)
- Brief Summary
2016 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/27645620 protocol 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34028800/ (added 04/06/2021)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 62
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
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 conf
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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
Name Time Method 1. Proportion of patients with undetectable minimal residual disease (MRD)<br>2. Overall response rate defined as complete or partial remission by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria<br>3. Progression-free survival at 2 years<br>4. Overall survival at 2 years<br>5. Time to MRD relapse in MRD negative patients<br>6. Safety and toxicity