Additional identifiers
EudraCT number
2015-003422-14
ClinicalTrials.gov number
Protocol/serial number
20572
Study information
Scientific title
CLARITY: Assessment of VenetoCLAx (ABT-199) in combination with IbRutInib in relapsed/refracTory Chronic LymphocYtic Leukaemia
Acronym
Study hypothesis
The aim of this study is to increase the effectiveness of ibrutinib by using it in combination with Venetoclax to assess if this is the ideal combination of drug to use and hope that patients can be treated with lower toxicity than standard treatments.
Ethics approval
Yorkshire & The Humber – Leeds East Research Ethics Committee, 21/12/2015, ref: 15/YH/0530
Study design
Multi-centre on-randomised study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Cancer; Subtopic: Cancer (Haematological Oncology); Disease: Leukaemia (Chronic Lymphocytic Leukaemia)
Intervention
Ibrutinib: Continuous Ibrutinib treatment of 420mg once daily
Venetoclax: Venetoclax treatment for a maximum of 24 months
Intervention type
Other
Phase
Drug names
Primary outcome measures
Proportion of patients with <0.01% MRD in the blood and bone marrow at 12 months.
Secondary outcome measures
1. Biological response is monitored throughout the duration of the trial
2. Overall Survival is determined from the date of registration to date of death
3. Progression-free survival (PFS) is monitored throughout the duration of the trial
4. Proportion of patients with <0.01% MRD in the blood and bone marrow is measured after 6 and 24 months of combination therapy
5. Response rate is determined using the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) criteria after 12 and 24 months of combination therapy
6. Toxicity of combination therapy is measured throughout the duration of trial
Overall trial start date
01/03/2016
Overall trial end date
01/12/2021
Reason abandoned
Eligibility
Participant inclusion criteria
1. Aged 18 and over
2. Able to give informed consent
3. Diagnosis of CLL, requiring therapy according to IWCLL criteria (appendix 1)
4. CLL should be assessable for MRD by flow cytometry (CD19, CD5 and CD23 and CD43 co-expression with weak CD20, CD79b/sIg & CD81 expression; to be confirmed by HMDS)
5. Refractory/relapsed CLL defined as any of the following:
5.1. Failure to achieve a response (CR or PR by IWCLL Criteria) to a purine analogue alone or in combination with chemotherapy
5.2. Relapse within 6 months of responding to a purine analogue alone or in combination with chemotherapy
5.3. Relapse at any time after the combination of fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine plus rituximab (or other equivalent monoclonal anti-CD20 antibodies)
5.4. Patients with CLL with deletion of chromosome 17p who have progressed after at least one previous therapy
6. ECOG performance status (PS) of 0, 1, or 2
7. Prepared to undergo the stipulated investigations within the trial (including bone marrow examinations)
8. Adequate bone marrow function (defined below) independent of growth factor or transfusion support, within 2 weeks of screening unless cytopenia is clearly due to marrow involvement of CLL:
8.1. Platelet count ≥ 75 x 109/L; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator), platelet count should be ≥ 30 109/L independent of transfusion
8.2. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L unless neutropenia is clearly due to marrow involvement of CLL (per the discretion of the investigator)
8.3. Total haemoglobin ≥ 90 g/L unless anaemia is due to marrow involvement of CLL (per the discretion of the investigator)
9. Adequate renal and hepatic function at screening:
9.1. Calculated creatinine clearance ≥ 50 mL/min using 24-hour creatinine clearance or modified Cockcroft-Gault equation (using ideal body mass [IBM] instead of mass): eCCR=((140-Age)>IBM (kg).[0.85 if female])/(72.Serum creatinine (mg/dL)) Or, if serum creatinine is in μmol/L: eCCR=((140-Age)>IBM (kg).[1.23 if male,1.04 if female])/( Serum creatinine (μmol/L)) IBM (kg) = ([height in cm−154] × 0.9)] + (50 if male, 45.5 if female)
10. AST or ALT≤ 3.0 times the upper limit of normal (ULN) of the institution's normal range
11. Bilirubin ≤ 1.5 × ULN. Patients with known Gilbert's syndrome may have a bilirubin level > 1.5 × ULN
12. Prothrombin time (or international normalised ratio) and partial thromboplastin time not to exceed 1.2 times the institution’s normal range
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 50; UK Sample Size: 50
Participant exclusion criteria
1. Transformation of CLL to aggressive NHL (e.g. Richter’s transformation, prolymphocytic leukaemia, or diffuse large B-cell lymphoma or CNS involvement by CLL)
2. A history of any severe, concurrent renal, neurological, psychiatric, endocrine, metabolic, immunologic, cardiac, pulmonary or hepatic diseases that could interfere with the patient’s ability to participate in the study
3. Use of prior investigational agents within 28 days of planned treatment
4. Females who are pregnant or lactating
5. Females of childbearing potential (or males whose partners are of childbearing potential) who are unwilling to use appropriate contraception during and for 3 months following treatment
6. Mantle cell lymphoma
7. Known to be HIV positive
8. Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology)
9. Positive test results for hepatitis C (HCV antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
10. Active secondary malignancy excluding basal cell carcinoma
11. Patients requiring or who have received anticoagulation treatment with warfarin or vitamin K antagonists within 1 week of registration
12. Patients requiring concomitant use of strong CYP3A4/5 inhibitors/inducers within 7 days prior to registration
13. Previous treatment with Ibrutinib, venetoclax or an alternative Btk or Bcl-2 inhibitor
14. Inability to tolerate uric acid reducing medications • Undergone an allogeneic stem cell transplant unless beyond 6 months post-transplant and off immune suppressive therapy with no evidence of Graft-versus-Host disease
15. Known hypersensitivity to either of the compounds or to its excipients
16. Patients who have received an anti-CLL monoclonal antibody within 8 weeks prior to registration
17. A cardiovascular disability status of New York Heart Association Class ≥ 3 (Class 3 is defined as cardiac disease in which patients are comfortable at rest but have marked limitation of physical activity due to fatigue, palpitations, dyspnoea or angina pain)
18. Major surgery within 30 days prior to registration
19. Vaccination with a live vaccine within 28 days prior to registration
20. Steroid therapy for anti-neoplastic intent will not be allowed either during or within 7 days prior to registration with the exception of inhalational steroids for the treatment of asthma or COPD, topical steroids, replacement corticosteroid therapy for an inherited or acquired deficiency
Recruitment start date
01/04/2016
Recruitment end date
01/12/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
Trial participating centre
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
Trial participating centre
Christie Hospital
550 Wilmslow Road
Manchester
M20 4BX
Trial participating centre
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Trial participating centre
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Trial participating centre
Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom
Trial participating centre
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
Trial participating centre
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Queen Elizabeth Medical Centre
Birmingham
B15 2TH
Trial participating centre
Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom
Trial participating centre
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Trial participating centre
St Batholomew’s Hospital
W Smithfield
London
EC1A 7BE
United Kingdom
Trial participating centre
St James’ Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Funders
Funder type
Government
Funder name
Leukaemia and Lymphoma Research
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary