Overview
Study of Ibrutinib + CD20 Antibody and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2031-09-30
2031-09-30
Target enrollment:
0
0
Participant gender:
All
All
Summary
The OASIS II trial is a multicentre, open label, randomized phase II trial. We will compare the efficacy of Ibrutinib/anti-CD20 Ab versus Ibrutinib/anti-CD20 Ab/Venetoclax given as fixed duration combinations in newly diagnosed Mantle Cell Lymphoma (MCL) patients (≥ 18 years and < 80 years of age). Treatment duration of Ibrutinib and Venetoclax will be a maximum of two years. Patients will be treated with CD20 Ab for 3.5 years. The primary aim is to assess MRD status at 6 months in both arms.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
The Lymphoma Academic Research OrganisationCollaborator:
Institute of Cancer Research, United KingdomTreatments:
Venetoclax
Criteria
Inclusion Criteria:1. Patient is ≥ 18 years and < 80 years of age at the time of signing the informed
consent form (ICF).
2. Patient understood and voluntarily signed and dated an ICF prior to any study-specific
assessments/procedures being conducted.
3. Patient willing and able to adhere to the study visit schedule and other protocol
requirements
4. Women of childbearing potential must have negative results for pregnancy test prior to
study treatment start and agree to abstain from breastfeeding during study
participation and at least 18 months after the last drug administration
5. Men or women of reproductive potential agree to use acceptable method of birth control
during treatment and for eighteen months after the last drug administration.
6. Histologically confirmed (according to the World Health Organization (WHO)
classification) mantle cell lymphoma. The diagnosis has to be confirmed by phenotypic
expression of CD5, CD20 and cyclin D1 or the t(11;14) translocation (by cytogenetics
and/or fluorescence in situ hybridization (FISH) and/or BCL1-IgH PCR)
7. Untreated MCL
8. Adequate renal function as demonstrated by a creatinine clearance > 50 mL/min;
calculated by Cockcroft Gault formula or Modification of Diet in Renal Disease (MDRD)
9. Adequate hepatic function per local laboratory reference range as follow:
- Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0 x upper limit
of normal (ULN)
- Bilirubin < 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
non-hepatic origin)
10. Stage II-IV disease, measurable with at least lymph node > 1.5 cm and requiring
treatment in the opinion of the treating clinician
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
12. Life expectancy of more than 3 months.
13. For France: patient affiliated to any social security system
Exclusion Criteria:
1. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
the New York Heart Association Functional Classification.
2. Impaired organ function (other than liver and renal) which will interfere with the
treatment
3. Hemoglobin level < 10g/dL; Neutrophil count <1 G/L; Platelets < 75 G/L (except if
related to lymphoma then platelet must be >50),
4. Major surgery within 28 days before enrollment
5. Known central nervous system lymphoma
6. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
7. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g.,
phenprocoumon)
8. Requires treatment with strong CYP3A inhibitors
9. Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID
vaccine)
10. Known history of human immunodeficiency virus (HIV)
11. Evidence of other clinically significant uncontrolled condition(s) including but not
limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note:
subjects with serologic evidence of prior vaccination to HBV (i.e. HBs antigen
negative, anti-HBs antibody + and antiHBc antibody -) and subjects with
anti-HB-core antibody that are HBV DNA negative may participate
12. Psychiatric illness or condition which could interfere with their ability to
understand the requirements of the study
13. Any life-threatening illness, medical condition, or organ system dysfunction which, in
the investigator' opinion, could compromise the patient safety, interfere with the
absorption or metabolism of treatment (Ibrutinib, CD20 Ab, venetoclax) or put the
study outcomes at undue risk
14. Pregnant, planning to become pregnant, or lactating woman
15. Known hypersensitivity to study treatment (CD20 Ab, Ibrutinib, Venetoclax) or to any
of the excipients
16. Known allergy to xanthine oxidase inhibitors or rasburicase
17. Known glucose-6-phosphate dehydrogenase (G6DP) deficiency
18. Known bleeding disorders
19. Severe prior reactions to monoclonal antibodies or with prior significant toxicity
(other than thrombocytopenia) from Bcl-2 inhibitor
20. History of prior other malignancy with the exception of:
- curatively treated basal cell carcinoma
- curatively treated squamous cell carcinoma of the skin or carcinoma in situ of
the cervix at any time prior to study
- other curatively treated cancer and patient disease-free for over 5 years
21. Anti-cancer therapies including chemotherapy, radiotherapy or other investigational
therapy, including targeted small molecule agents
22. Biological agents (e.g. monoclonal antibodies) for anti-neoplastic intent: excluded 30
days prior to first dose of venetoclax
23. Person deprived of his/her liberty by a judicial or administrative decision
24. Adult person under legal protection