A study comparing intermittent with continuous treatment with ibrutinib in chronic lymphocytic leukaemia (CLL)
- Conditions
- Chronic lymphocytic leukaemia (CLL)Cancer
- Registration Number
- ISRCTN51675454
- Lead Sponsor
- niversity of Leeds
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 830
Trial Registration Inclusion Criteria:
1. At least 18 years old
2. A diagnosis of chronic lymphocytic leukaemia (CLL) or small lymphocyticlymphoma (SLL) (by 2018 iwCLL criteria)
3. World Health Organisation (WHO) performance status (PS) of 0,1 or 2
4. Biochemical values must be within the following limits within 4 weeks prior to randomisation/or registration for the Clinical Need Cohort and at baseline:
4.1. Alanine aminotransferase (ALT) =3 x upper limit of normal (ULN) OR Aspartate aminotransferase (AST) =3 x ULN.
4.2. Total bilirubin =1.5 x ULN, unless bilirubin rise is due to Gilbert’s syndrome or of non hepatic origin
5. Agree to follow the pregnancy prevention plan*
6. Able to provide informed consent
*Participants randomised to the pause/resume arm must adhere to this whilst receiving ibrutinib, but will not be required to follow contraceptive measures during the planned treatment breaks
Additional inclusion criteria for participants in the Clinical Need Cohort:
1. Meet all of the Registration Inclusion criteria
2. Currently receiving ibrutinib and nearing the end or having completed 6 years of ibrutinib treatment on FLAIR**
3. Have signs of progressive or returning CLL after completing 6 years of ibrutinib treatment within FLAIR, but prior to entry into STATIC
Additional inclusion criteria for Front Line participants entering the randomisation trial:
1. Meet all of the Registration Inclusion criteria
2. Currently receiving ibrutinib in FLAIR or having completed 6 years of ibrutinib of ibrutinib in FLAIR**
3. In clinical remission all of the following:
3.1. No palpable lymph nodes;
3.2. No palpable spleen; and
3.3. Lymphocyte count below 5x10^9/L continuously for at least the 12 months before randomisation
**Patients should enter STATIC on completion of treatment in FLAIR, with no break in therapy, with the exception of participants who have completed the 6 years of treatment in FLAIR prior to STATIC opening
Additional inclusion criteria for Previously Treated participants entering the randomisation trial:
1. Meet all of the registration inclusion criteria
2. Currently receiving ibrutinib for at least the previous 36 months. There is no restriction on maximum duration of treatment prior to enrolment.
3. In clinical remission fulfilling all of the following:
3.1. No palpable lymph nodes;
3.2. No palpable spleen; and
3.3. Lymphocyte count below 5x10^9/L continuously for at least the 12 months before randomisation
Trial Registration Exclusion Criteria:
1. Pregnant females
2. Known intolerance or hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
3. Receipt of live vaccination within 4 weeks prior to registration and for the duration of the study.
4. History or current evidence of Richter’s transformation
5. Major surgery within 4 weeks prior to randomisation/or registration for the Clinical Need Cohort
6. Active infection
7. Concomitant warfarin (or equivalent vitamin K inhibitor)
8. Central nervous system involvement with CLL
9. Cardiac failure; including symptomatic cardiac failure not controlled by therapy,or unstable angina not adequately controlled by current therapy (in patients with a significant cardiac history the left ventricular function should be assessed and patients with severe impairment should be excluded)
10. Respiratory impairment (e.g. bronchiectasis or severe COPD)
11. Other severe, concurrent diseases or mental disorders that could interfere with their ability to participate in the study
12. 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),aHB DNA test will be performed and if positive the patients will be excluded. During treatment, these participants should be monitored and managed to prevent HBV reactivation.
13. Positive serology for Hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a test for hepatitis C RNA (for example HCV RNA PCR). If positive the patients will be excluded.
14. Persisting severe pancytopenia (neutrophils <0.5 x 109/L or platelets <50 x 109/L)unless due to direct marrow infiltration by CLL
15. Current treatment with prednisolone of >20mg/day
16. Uncontrolled Active haemolysis
17. History of stroke or intracranial haemorrhage within 6 months prior to enrolment.
18. Requirement for treatment with a strong CYP3A inhibitor or inducer
19. New treatment with two or more antiplatelet drugs, treatment that has been administered at a stable dose for at least 3 months prior to registration is permissible
20. Current treatment with any concomitant ACE inhibitors
Additional exclusion criteria for participants in the Clinical Need Cohort:
1. Meet none of the registration exclusion criteria
2. Active Disease, as per the 2018 iwCLL criteria requiring an alternative therapy.
3. Received treatment other than ibrutinib for CLL since completing FLAIR
4. Be eligible for front-line randomisation
Additional exclusion criteria for Front-Line participants entering the randomisation trial:
1. Meet none of the registration exclusion criteria
2. Disease progression (according to 2018 iwCLL criteria)
3.Ibrutinib treatment break for toxicity/patient choice for more than 28 days in last12 months
Additional exclusion criteria for Previously Treated participants entering the randomisation trial:
1. Meet none of the registration exclusion criteria
2. Disease progression (according to 2018 iwCLL criteria)
3. Ibrutinib treatment break for toxicity/patient choice for more than 28 days in last12 months
4. Any illness,disease or condition,such as active cancer or secondary primary malignancy (SPM),with a prognosis of less than 5 years
5. Patients with a creatinine clearance of less than 30ml/min (either measured or derived by the Cockcroft Gault formula or alternative locally approved formula).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time to treatment strategy failure. Time to treatment strategy failure is defined as the time from randomisation to time of treatment strategy failure. Treatment strategy failure is defined as the first documented instance of active disease that does not respond to treatment, or death from any cause measured using patient records throughout the study
- Secondary Outcome Measures
Name Time Method