Trial Title:
Zanubrutinib Plus Rituximab for Patients With Indolent Mantle Cell Lymphoma
NCT ID:
NCT05635162
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Rituximab
Zanubrutinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomised
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zanubrutinib
Description:
Zanubrutinib dose is 160 mg twice daily (BD) orally (PO) on days 1-28 of each 28-day
cycle.
Arm group label:
Arm B: Experimental
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab 375 mg/m2 intravenous (IV)* on day 1 (+/-3 days) of each 28-day cycle
Arm group label:
Arm B: Experimental
Summary:
Phase II, multicentre, randomised, open-label study to assess the benefit of early
intervention with fixed duration, time-limited zanubrutinib-rituximab in indolent mantle
cell lymphoma (MCL)
Detailed description:
This is a phase II, multicentre, randomised open label study to assess the safety and
efficacy of zanubrutinib in combination with rituximab for previously untreated indolent
MCL patients.
50 patients will be recruited from 15 UK centres over 30 months.
Enrolled patients will be randomised (1:1) to ongoing observation (control arm; arm A) or
fixed-duration zanubrutinib-rituximab (experimental arm; arm B). Patients will
discontinue zanubrutinib-rituximab after 6 cycles of therapy or sooner in the advent of
unacceptable toxicity or any other reason.
All patients will be followed up for a minimum of 2 years after randomisation. Patients
in arm B who develop disease progression and require further therapy after the initial
time-limited Zanu-R will receive standard of care therapy according to front line
treatment available at that time.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 18 years of age or over.
2. Life expectancy ≥ 6 months.
3. Pathologically confirmed MCL, with documentation of monoclonal B cells that have a
chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, D2 or D3.
4. Stage II-IV MCL measurable by CT imaging or by white cell count (WCC)/BM
infiltration.
5. 'Indolent' MCL, defined as 1 or more of the following:
- Observation with no treatment for a minimum of 6 months after the initial
diagnosis
- Leukaemic non-nodal variant (lymphocytosis/splenomegaly only without nodal
involvement)
- Low tumour volume (largest lymph node ≤ 3cm in maximal diameter), proliferation
fraction (Ki67 or equivalent) ≤30% and classical morphology
(non-blastoid/pleomorphic)
6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
7. Absolute neutrophil count ≥1.0 x 109/L and platelets ≥75 x 109/L independent of
growth factor support.
8. AST and/or ALT ≤3 x upper limit of normal (ULN).
9. Total Bilirubin ≤1.5 x ULN unless due to Gilberts syndrome or of non-hepatic origin
unless directly attributable to the patient's MCL.
10. Calculated creatinine clearance ≥30 mL/min. Glomerular filtration rate (GFR) ≥30
mL/min directly measured with 24 hour urine collection, or creatinine clearance
calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈
((140 - age) x bodyweight)/ (72 x creatinine), for women x 0, 85).
11. Able to give voluntary written informed consent.
12. Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty.
13. Negative serum or urine pregnancy test for women of childbearing potential (WOCBP).
14. Willing to comply with the contraceptive requirements of the trial.
Exclusion Criteria:
1. Any prior therapy for MCL, including prior radiotherapy.
2. Central nervous system (CNS) involvement of MCL.
3. Uncontrolled infection with HIV or any uncontrolled active systemic infection (e.g.,
bacterial, viral or fungal). Patients with well-controlled HIV status (undetectable
viral load) will not be excluded.
4. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody
(anti-HB core) positive and who are surface antigen (HBsAg) negative will need to
have a negative polymerase chain reaction (PCR) test. Those who are hepatitis B
HbsAg positive or hepatitis B PCR positive will be excluded. Those who are hepatitis
C antibody and PCR positive will be excluded (those who are hepatitis C antibody
positive and PCR negative will not be excluded).
5. No progression requiring treatment since initial diagnosis.
6. Vaccinated with live vaccines (not including messenger ribonucleic acid (mRNA),
viral vector or other non-live COVID19 vaccines) within four weeks prior to
randomisation.
7. Major surgical procedure within 28 days prior to randomisation. Note: If a subject
had major surgery, they must have recovered adequately from any toxicity and/or
complications from the intervention before the first dose of study drug.
8. 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.
9. Requirement for moderate or strong CYP3A inducers. Moderate and strong CYP3A
inhibitors are allowed although these should be switched to agents causing less
CYP3A inhibition where possible.
10. Requirement for vitamin K antagonists (alternative anticoagulation is allowed (e.g.
DOACs), but patients must be properly informed about the potential risk of bleeding
alongside zanubrutinib). Requires ongoing treatment with warfarin or warfarin
derivatives
11. Active bleeding or history of bleeding diathesis (e.g. haemophilia or von Willebrand
disease) or history of spontaneous bleeding requiring blood transfusion or other
medical intervention.
12. Clinically significant cardiovascular disease such as uncontrolled arrhythmias, or
history of ventricular tachycardia, ventricular fibrillation, torsades de points or
myocardial infarction within 6 months of randomisation, or any Class 3 or 4 cardiac
disease as defined by the New York Heart Association (NYHA) Functional
Classification, or corrected QT interval (QTc) > 480 msec, second-degree
atrioventricular block Type II, third-degree atrioventricular block at
randomisation, unstable angina within 3 months prior to randomisation.
13. History of stroke or intracranial haemorrhage within 6 months prior to
randomisation.
14. Any other severe medical or psychiatric illness that in the opinion of the
investigator would interfere with participation in this clinical study.
15. Malabsorption syndrome, unable to swallow capsules, 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.
16. Women who are pregnant or breastfeeding.
17. Male participants with female partners of childbearing potential who are unwilling
to use appropriate contraception methods.
18. Concurrent treatment with another investigational agent.
19. History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies, known sensitivity or allergy to murine products.
20. Known hypersensitivity to any active substance or to any of the excipients of one of
the drugs used in the trial.
21. Severe or debilitating pulmonary disease.
22. Underlying medical conditions that, in the investigator's opinion, will render the
administration of study drug hazardous or obscure the interpretation of toxicity or
AEs
23. Concurrent participation in another therapeutic clinical trial.
24. Active and/or ongoing autoimmune anaemia and/or autoimmune thrombocytopenia (eg.
idiopathic thrombocytopenia purpura).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Clatterbridge Cancer Centre
Address:
City:
Liverpool
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Matt Wells
Facility:
Name:
St Bartholomew's Hospital
Address:
City:
London
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Rebecca Auer
Facility:
Name:
University College London Hospital
Address:
City:
London
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Maria Marzolini
Facility:
Name:
Christie Hospital
Address:
City:
Manchester
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Kim Linton
Facility:
Name:
Churchill Hospital
Address:
City:
Oxford
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Toby Eyre
Start date:
May 17, 2024
Completion date:
October 2028
Lead sponsor:
Agency:
University College, London
Agency class:
Other
Collaborator:
Agency:
BeiGene
Agency class:
Industry
Source:
University College, London
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05635162
