Assessment of venetoclax in combination with Ibrutinib in patients with Chronic Lymphocytic Leukaemia
| ISRCTN | ISRCTN13751862 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13751862 |
| EudraCT/CTIS number | 2015-003422-14 |
| Secondary identifying numbers | 20572 |
- Submission date
- 09/03/2016
- Registration date
- 09/03/2016
- Last edited
- 05/01/2024
- 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
Ms Rebecca Bishop
Public
Public
University of Birmingham
Institute for Cancer studies
Edgbaston
Birmingham
B15 2TT
United Kingdom
Study information
| Study design | Multi-centre non-randomised study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | CLARITY: Assessment of VenetoCLAx (ABT-199) in combination with IbRutInib in relapsed/refracTory Chronic LymphocYtic Leukaemia |
| Study acronym | CLARITY |
| Study objectives | 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(s) | Yorkshire & The Humber – Leeds East Research Ethics Committee, 21/12/2015, ref: 15/YH/0530 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure | 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 study start date | 01/03/2016 |
| Completion date | 29/10/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 50; UK Sample Size: 50 |
| Total final enrolment | 53 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/04/2016 |
| Date of final enrolment | 01/12/2017 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
Belfast
BT9 7AB
United Kingdom
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Christie Hospital
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
Hammersmith Hospital
Du Cane Road
London
W12 0HS
United Kingdom
London
W12 0HS
United Kingdom
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
London
SE5 9RS
United Kingdom
Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Queen Elizabeth Hospital
Queen Elizabeth Medical Centre
Birmingham
B15 2TH
United Kingdom
Birmingham
B15 2TH
United Kingdom
Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom
Liverpool
L7 8XP
United Kingdom
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
St Bartholomew’s Hospital
W Smithfield
London
EC1A 7BE
United Kingdom
London
EC1A 7BE
United Kingdom
St James’ Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
Leeds
LS9 7TF
United Kingdom
Sponsor information
University of Birmingham
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 29/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 20/10/2019 | 11/06/2020 | Yes | No |
| Plain English results | 23/02/2021 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No | ||
| Basic results | version 1.0 | 03/01/2024 | 05/01/2024 | No | No |
Additional files
Editorial Notes
05/01/2024: The basic results have been uploaded as an additional file.
17/05/2023: The following changes have been made:
1. The overall study end date has been changed from 03/05/2023 to 29/10/2022.
2. The intention to publish date has been changed from 03/05/2024 to 29/10/2023.
22/04/2022: The following changes have been made:
1. The overall trial end date has been changed from 01/04/2022 to 03/05/2023.
2. The intention to publish date has been changed from 01/04/2023 to 03/05/2024.
14/12/2021: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/12/2021 to 01/04/2022.
2. The intention to publish date was changed from 01/12/2022 to 01/04/2023.
20/09/2021: Internal review.
23/02/2021: Cancer Research UK lay results summary link added to Results (plain English).
11/06/2020: Publication reference and total final enrolment number added.
01/11/2017: Internal review.
06/07/2016: Link to Cancer Help UK lay summary added.
11/03/2016: Verified study information with principal investigator.
