Clinical Trials

Summary of NCRI CLL Trials Portfolio ~ January 2020:

Compiled with the assistance of Dr S Lyengar, Consultant Haematologist, RoyalMarsden Hospital.

  Currently Open or soon to Open Trials Future Planned Trials
Patients considered fit for FCR (previously untreated)

CLL10 (FLAIR) – Phase III

FCR vs Ibrutinib monotherapy vs Ibrutinib+venetoclax.

(FCRvR+I arm closed in July 2018.)

Recruitment scheduled to close Aug/Sep 2020

 

ERASE CLL (in set up)
Patients considered unfit for FCR (previously untreated)

 

 

 

 

17p deleted CLL (previously untreated)

 FLAIR I+V arm for 17p/P53mutated (scheduled to close in 2021)

 

BGB-311-304. Phase 3, Randomized Study of Zanubrutinib v Bendamustine with Rituximab

 

 

Consolidation/Maintenance

 

 
Stage A CLL

OXLORED Observational Study

 

 

Richter’s Transformation

Frontline and relapsed

STELLAR: CHOP-R vs CHOP-R in combination with ACP-196 Bloodwise TAP Trial

 

 
Relapsed/Refractory CLL

BeiGene BGB-3111-305

Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared with Ibrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Zuma-8 CAR-T Cell Trial
Relapsed/Refractory CLL (cont)

Phase 1/Phase 2 ATRi + Acalabrutinib study (ACE-CL-110)

 

SNS-062 (Sunesis) Phase 1/Phase 2 dose escalation and cohort expansion study of SNS062 in patients with B cell malignancies. (Open in 2020?)

 

 
Relapsed 17p del CLL

Phase 1/Phase 2 ATRi + Acalabrutinib study (ACE-CL-110)

 

SNS-062 (Sunesis) Phase 1/Phase 2 dose escalation and cohort expansion study of SNS062 in patients with B cell malignancies. (Open in 2020?)

 

Zuma-8 CAR-T Cell Trial

 

T-Prolymphocytic Leukaemia (T-PLL)

AbbvieT-PLL study scheduled to open Q2 2020 Single arm Phase 2 study of Venetoclax + Ibrutinib in relapsed/refractory T-PLL

 

 

 

CLL10 FLAIR

Phase III randomised trial to assess whether Ibrutinib+Rituximab or Ibrutinib + Venetoclax or Ibrutinib monotherapy is superior to Fludarabine, Cyclophosphamide and Rituximab (FCR) in terms of progression-free survival and secondary objectives overall survival, response, minimal residual disease negativity and relapse, toxicity, quality of life and health economics. Previously untreated patients are eligible if they are considered fit for FCR.

The FCR v Ibrutinib +Rituximab arm stopped in July 2018

The trial is sponsored by the Leeds Teaching Hospitals.

http://medhealth.leeds.ac.uk/LICTR /flair

http://www.cancerresearchuk.org/about-cancer/trials/a-trial-ibrutinib-rituximab-chronic-lymphocytic-leukaemia-flair

http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=16675

 

STELLAR

A Phase II, randomised study of CHOP-R in combination with Acalabrutinib (an oral BTK inhibitor) compared to CHOP-R in patients with newly diagnosed Richter’s Syndrome (RS) followed by an extension study to evaluate Acalabrutinib and other novel therapies in relapsed/refractory RS

The trial is managed by the Cancer Research UK Clinical Trials Unit at the University of Birmingham.

This research is being funded by Bloodwise as part of the Trials Acceleration Program (TAP) and by Acerta Pharma.

Currently recruiting at:

  • Oxford Churchill Hospital
  • St James Hospital Leeds
  • Beatson WOSCC
  • Belfast City Hospital
  • Clatterbridge Cancer Centre
  • Kings College Hospital
  • Leicester Royal Infirmary
  • Nottingham City Hospital
  • Queen Elizabeth Birmingham
  • Royal Bournemouth Hospital
  • Sheffield Hallam Hospital
  • Southampton General
  • St Bartholomew’s Hospital
  • The Christie
  • University Hospital of Wales
  • University College London

 

ACE-CL-110

A Study Investigating AZD6738 Monotherapy (ATR Inhibitor) and Acalabrutinib in Combination With AZD6738  in Subjects With Relapsed or Refractory High-risk Chronic Lymphocytic Leukemia (CLL)

AZD6738 is an oral ATR kinase inhibitor.

Acalabrutinib is a new generation oral BTK inhibitor.

See: https://clinicaltrials.gov/ct2/show/NCT03328273

An International Trial sponsored by Acerta Pharma BV and currently recruiting in the UK at:

  • Leeds Teaching Hospitals NHS Trust
  • University of Oxford
  • Nottingham University Hospitals NHS Trust
  • Cardiff and Vale UHB Headquarters
  • Cambridge University Hospitals NHS Trust
  • The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
  • King’s College London
  • Barts Health NHS Trust
  • University College London (UCL) – Cancer Research UK & UCL Cancer Trials Centre
  • University of Southampton
  • University of Birmingham
  • University of Liverpool

 

BGB-3111-304

A randomised phase 3 trial comparing Zanubrutinib (a new oral BTK inhibitor)with Bendamustine with Rituximab for patients with untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).

This is an international trial sponsored by BeiGene and at present is only recruiting people with CLL who have a 17p deletion. Trial is currently recruiting at:

 

Leeds Teaching Hospitals NHS Trust

 

See also www.clinicaltrials.gov/ct2/show/study/NCT03336333

 

BGB-3111-305

A randomised phase 3 trial comparing Zanubrutinib (a new oral BTK inhibitor)with Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).

  • This is an international trial sponsored by BeiGene and at present recruiting in the UK at:
  • Aberdeen Royal Infirmary – PPDS
  • Norfolk and Norwich University Hospital
  • Royal Bournemouth Hospital
  • Sunderland Royal Hospital
  • GenesisCare – Oxford
  • Birmingham Heartlands Hospital
  • Kent and Canterbury Hospital
  • St James University Hospital
  • Barts Health NHS Trust
  • Kings College Hospital
  • The Christie NHS Foundation Trust – PPDS
  • Nottingham University Hospitals NHS Trust
  • Derriford Hospital
  • Southampton General Hospital

See also  https://clinicaltrials.gov/ct2/show/NCT03734016

 

OXLORED Study

This is a study to identify the clinical, genomic and immunological predictive markers of progression to malignant disease.

It will be open to individuals diagnosed in the last 2 years with high count MBL, Binet Stage A CLL, IgG/ IgG/ IgM MGUS, asymptomatic WM not requiring treatment, and smouldering myeloma not requiring treatment.

The study does not involve any treatment and is being undertaken by the University of Oxford.

See also www.clinicaltrials.gov/ct2/show/NCT04023747

 

SNS-062 (Sunesis)

This is a phase 1/2 study to evaluate the safety of Vecabrutinib (SNS-062) in B lymphoid cancers including CLL.

The study is sponsored by Sunesis Pharmaceuticals and is due to open  in the UK for a limited number of patients in 2020.

https://www.clinicaltrials.gov/ct2/show/NCT03037645?term=SNS-062&rank=1

 

ERASE

ERAdication of minimal residual disease by SEq uencing therapy in patients with Chronic Lymphocytic Leukaemia (CLL).

ERASE CLL is currently in set up and will be a national, multi-centre, response-guided, phase III, open-label, randomised controlled trial for patients with Chronic Lymphocytic Leukaemia (CLL) requiring front-line treatment. The overarching aim of the trial is to develop a therapeutic strategy to cure CLL.

The Primary objectives of the trial will be to:

  1. To assess whether a fixed-duration doublet combination of BTKi and BCL-2i is superior to a doublet of venetoclax and obinutuzumab in terms of MRD negativity.
  2. Subsequently, for participants who remain MRD positive after initial treatment with a fixed-duration doublet combination of BTKi and BCL-2i:

To assess whether the addition of anti-CD20 antibody for a fixed duration in a triplet is superior to further fixed duration treatment with a doublet of BTKi and BCL-2i in terms of MRD negativity.

Trial currently in set up.

Trial sponsored by the University of Leeds

 

Additional information about trials can be found on the following web sites:

 Bloodwise

Lymphoma Action

Cancer Research UK

USA

 

GWB

January 2020