Front-line therapy in CLL: assessment of ibrutinib-containing regimes | Recruiting
Front-line therapy in CLL: assessme... | Recruiting
Front-line therapy in CLL: assessment of ibrutinib-containing regimes
FLAIR

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Medical Conditions
  • Topic: Cancer
  • Subtopic: Haematological Oncology
  • Disease: Leukaemia (chronic)
Primary Contact Details
Mr Jamie Oughton
+44 (0)113 343 1494
See all trial contact details
Recruitment Status
Recruiting
Trial source and source ID number
ISRCTN01844152
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
http://www.cancerresearchuk.org/about-cancer/trials/a-trial-ibrutinib-rituximab-chronic-lymphocytic-leukaemia-flair
Research Details
  • The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of progression-free survival.
Phase
Not Applicable
Study Design
Randomised; Interventional; Design type: Treatment
Study Type
Interventional
Intervention

Current interventions as of 29/06/2017:
Participants will be randomised on a 1:1:1:1 basis to receive standard therapy with fludarabine, cyclophosphamide and rituximab (FCR), ibrutinib plus rituximab (IR), ibrutinib monotherapy (I) or ibrutinib + venetoclax (I+V).

Added 24/07/2017:
FCR: fludarabine (oral), cyclophosphamide (oral) and rituximab (intravenous infusion). F (24mg/m2/day) and C (150mg/m2/day) are administered days 1-5 and R is administered at 375mg/ m2 for day 1 cycle 1 and then at 500mg/m2 for day 1 for cycles 2-6. Each cycle is repeated every 28 days and there are 6 cycles.
IR: ibrutinib (oral) and rituximab. 6 cycles of R as per FCR. Ibrutinib (420mg) is administered daily for six years.
I: ibrutinib monotherapy is administered as per IR
I+V: ibrutinib + venetoclax (oral): ibrutinib is administered as per IR. Venetoclax is given daily from week 9 onwards in weekly dose increments (20mg, 50mg, 100mg, 200mg and 400mg) after which 400mg is administered for six years.
Follow up: baseline, 9 months post randomisation then every six months until 7 years or disease progression. All participants will be followed up at least annually until death.

Previous interventions:
Participants will be randomised on a 1:1 basis to receive standard therapy with fludarabine, cyclophosphamide and rituximab (FCR) or ibrutinib plus rituximab (IR).

Intervention Type
Drug
Primary Outcome Measures
    The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of progression-free survival, and whether IR toxicity rates are favourable.
Secondary Outcome Measures
    1. Overall survival
    2. Undetectable minimal residual disease
    3. Response to therapy
    4. Health-related quality of life
    5. Cost-effectiveness
Publication(s)
2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28830517
Result Reports
Sorry, this information is not available
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
Both
Age Range
Adult
Who Can Participate
Patient
Number of Participants
Planned Sample Size: 1576; UK Sample Size: 1576
Participant Inclusion Criteria
    1. At least 18 years old. Maximum age of 75 years old.
    2. B-CLL with a characteristic immunophenotype, including small lymphocytic lymphoma
    3. Binet’s Stages C, B or Progressive Stage A
    4. Requiring therapy by the IWCLL criteria in that they must have at least one of the following:
    4.1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.
    4.2. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
    4.3. Massive nodes (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
    4.4. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months as long as the lymphocyte count is over 30 x 10^9/L
    4.5. A minimum of any one of the following disease-related symptoms must be present:
    4.5.1. Unintentional weight loss more than or equal to 10% within the previous 6 months.
    4.5.2. Significant fatigue (i.e. Eastern Cooperative Oncology Group PS 2 or worse; cannot work or unable to perform usual activities)
    4.5.3. Fevers of greater than 38.0°C for 2 or more weeks without other evidence of infection
    4.5.4. Night sweats for more than 1 month without evidence of infection
    5. Considered fit for treatment with FCR as determined by the treating clinician
    6. World Health Organisation (WHO) performance status (PS) of 0, 1 or 2
    7. Able to provide written informed consent
    8. Biochemical values must be within the following limits within 14 days prior to randomization and at baseline:
    8.1. Alanine aminotransferase (ALT) 3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) 3 x ULN.
    8.2. Total bilirubin = 1.5 x ULN, unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
Participant Exclusion Criteria
    1. Prior therapy for CLL
    2. History or current evidence of Richter’s transformation
    3. Major surgery within 4 weeks prior to randomisation
    4. Active infection
    5. Above 20% P53 deletion, determined by FISH
    6. Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies
    7. Concomitant warfarin or equivalent vitamin K inhibitor - added 29/06/2017: or other oral anticoagulant treatment; anyone requiring anticoagulation treatment for greater than 6 months is not eligible for trial entry
    8. Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment with rituximab has finished, or 30 days after treatment with ibrutinib has finished, whichever is latest. Women must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction
    9. 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 with rituximab has finished, or 3 months after treatment with ibrutinib has finished, whichever is latest, unless they are surgically sterile
    10. CNS involvement with CLL
    11. 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)
    12. Respiratory impairment (bronchiectasis or moderate COPD)
    13. Other severe, concurrent diseases or mental disorders that could interfere with their ability to participate in the study
    14. Inability to swallow oral medication
    15. Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease etc)
    16. Known HIV positive
    17. 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
    18. 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
    19. History of prior malignancy, with the exception of the following:
    19.1. Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
    19.2. Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
    19.3. Adequately treated cervical carcinoma in situ without current evidence of disease
    20. Persisting severe pancytopenia (neutrophils <0.5 x 10^9/l or platelets <50 x 10^9/l) unless due to direct marrow infiltration by CLL
    21. Current treatment with prednisolone of >10 mg/day
    22. Active haemolysis (patients with haemolysis controlled with prednisolone at a dose 10 mg or less per day can be entered into the trial)
    23. Patients with a creatinine clearance of less than 30 ml/min (either measured or derived by the Cockcroft Gault formula or alternative locally approved formula)
    24. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
    25. Requirement for treatment with a strong CYP3A4/5 inhibitor or inducer
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
Leeds
LS2 9JT
-
Trial Contact(s)
Primary Trial Contact
Mr Jamie Oughton
+44 (0)113 343 1494
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
FLAIR: Front-Line therapy in CLL: Assessment of Ibrutinib-containing Regimes: a randomised controlled trial
EudraCT Number
2013-001944-76
Funder(s)
  • Cancer Research UK
  • Grant Codes: C18027/A15790
  • Janssen Pharmaceuticals
  • AbbVie Ltd
Other Study ID Numbers
16675
Sponsor(s)
University of Leeds (UK)
Key Dates

Recruitment Start Date

01 Sep 2014

Recruitment End Date

01 Jan 2020

Trial Start Date

01 Aug 2014

Trial End Date

01 Jan 2030

Date added to source

08 Aug 2014

Date updated in source

19 Oct 2017