Condition category
Cancer
Date applied
09/03/2016
Date assigned
09/03/2016
Last edited
06/07/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Ms Rebecca Bishop

ORCID ID

Contact details

University of Birmingham
Institute for Cancer studies
Edgbaston
Birmingham
B15 2TT
United Kingdom

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

Sponsor information

Organisation

University of Birmingham

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Publication citations

Additional files

Editorial Notes

06/07/2016: Link to Cancer Help UK lay summary added. 11/03/2016: Verified study information with principal investigator.