NCT05004064

Brief Summary

This is a phase II, single-arm, open-label, multicentre study of acalabrutinib and rituximab for elderly or frail patients with previously untreated mantle cell lymphoma.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P25-P50 for phase_2

Timeline
31mo left

Started Nov 2023

Longer than P75 for phase_2

Geographic Reach
1 country

12 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress50%
Nov 2023Dec 2028

First Submitted

Initial submission to the registry

June 8, 2021

Completed
2 months until next milestone

First Posted

Study publicly available on registry

August 13, 2021

Completed
2.3 years until next milestone

Study Start

First participant enrolled

November 30, 2023

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2026

Expected
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

April 9, 2025

Status Verified

October 1, 2024

Enrollment Period

3 years

First QC Date

June 8, 2021

Last Update Submit

April 7, 2025

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Overall response rate

    To determine the efficacy of acalabrutinib in combination with rituximab in terms of disease response.

    24 weeks

Secondary Outcomes (4)

  • Progression free survival

    From the date of first dose of acalabrutinib until the date of progression or death. Assessed up to 42 months.

  • Overall survival

    From the date of first dose of acalabrutinib until the date of death. Assessed up to 42 months.

  • Quality of life up to 24 months

    At baseline, week 12, week 24, month 12 and month 24

  • Incidence and frequency of grade 1-2 and 3+ adverse events seen in both treatment arms.

    Between the start of study treatment and 30 calendar days post last IMP administration.

Study Arms (1)

Acalabrutinib and rituximab

EXPERIMENTAL

Patients with untreated mantle cell lymphoma will receive acalabrutinib and rituximab for up to six cycles. Each cycle will comprise of acalabrutinib 100mg twice daily orally for 28 days and rituximab 375mg/m2 IV on day 1 (+/1 3 days) of every cycle.

Drug: AcalabrutinibDrug: Rituximab

Interventions

AcalabrutinibDRUG

Patients will receive acalabrutinib 100mg twice daily for up to six 28 day cycles. Patients can receive 100mg once daily for cycle 1, day 1 to day 7, according to the investigator's discretion.

Acalabrutinib and rituximab
RituximabDRUG

Patient will receive rituximab 375 mg/m2 IV on day 1 (+/- 3 days) of each cycle, for a maximum of 6 cycles

Acalabrutinib and rituximab

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women ≥ 60 years of age.
  • Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
  • Stage II-IV MCL and requiring treatment in the opinion of the treating clinician.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-3
  • One or more of the following:
  • Age 80 years or more
  • Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score 6 or greater
  • Left ventricular ejection fraction (LVEF) less than or equal to 50% as assessed by echocardiogram
  • Significant co-morbidities or cardiac risk factors making anthracycline-containing chemotherapy inadvisable
  • Heart failure clinically determined by the presence of New York Heart Association (NYHA) failure grade II due to a cause other than MCL
  • Impaired respiratory function with DLCO and/or FVC/FEV1 ratio less than 75% of predicted due to a cause other than MCL
  • Significant respiratory illness e.g. moderate chronic obstructive pulmonary disease (COPD) bronchiectasis
  • Other co-morbidities that in the Investigator's opinion which would preclude the use of standard full dose immuno-chemotherapy (to be discussed on a case-by-case basis with the TMG, via UCL CTC)
  • Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules/tablets without difficulty.
  • Negative serum or urine pregnancy test for women of childbearing potential (WOCBP).
  • +2 more criteria

You may not qualify if:

  • Any prior therapy (including targeted inhibitors) for MCL (other than prior localised radiotherapy, a 10-day pulse of high dose steroids or continuous prednisolone above 20mg od or equivalent for symptom control).
  • Patients considered by the investigator fit enough to receive standard, full dose cytotoxic immunochemotherapy as treatment for non-transplant eligible MCL e.g., full dose R-CHOP, VR-CAP, R-Bendamustine, R-FC.
  • Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localised prostate cancer or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to \< 5 years.
  • Clinically significant cardiovascular disease such as uncontrolled arrhythmias, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification (33), or corrected QT interval (QTc) \> 480 msec at screening.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  • Known history of infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral or fungal).
  • Known history of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components).
  • Active bleeding or history of bleeding diathesis (e.g. haemophilia or von Willebrand disease).
  • Uncontrolled AIHA (autoimmune haemolytic anaemia) or ITP (idiopathic thrombocytopenic purpura).
  • Known presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
  • Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days prior to the first dose of study drug.
  • Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) \> 2 x upper limit of normal (ULN).
  • Requires treatment with proton pump inhibitors (e.g. omeprazole, esomeprazole, lansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrolment to this study.
  • History of significant cerebrovascular disease/event, including stroke or intracranial haemorrhage, within 6 months before the first dose of study drug.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

The Royal Bournemouth Hospital

Bournemouth, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, United Kingdom

RECRUITING

Royal Cornwall Hospital

Cornwall, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

RECRUITING

St. Bartholomew's Hospital

London, United Kingdom

RECRUITING

University College London Hospital

London, United Kingdom

RECRUITING

The Christie Hospital

Manchester, United Kingdom

RECRUITING

Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, United Kingdom

RECRUITING

Norfolk and Norwich University Hospital

Norwich, United Kingdom

RECRUITING

Cancer and Haematology Centre, Churchill Hospital

Oxford, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, United Kingdom

RECRUITING

Royal Stoke Hospital

Stoke-on-Trent, United Kingdom

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

acalabrutinibRituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Toby Eyre

    Churchill Hospital, Oxford, United Kingdom

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Max McLaughlin Callan

CONTACT

020 7679 5531ctc.caramel@ucl.ac.uk

Marissa Arfan

CONTACT

020 7679 9855ctc.caramel@ucl.ac.uk

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 8, 2021

First Posted

August 13, 2021

Study Start

November 30, 2023

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

December 1, 2028

Last Updated

April 9, 2025

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will not share

Locations

GB(12)