Study of Ibrutinib + CD20 Antibody and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

A Randomized Phase II Trial Evaluating Ibrutinib Plus CD20 Ab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Ibrutinib 560 mg; Drug: Venetoclax 10 MG Oral Tablet [Venclexta]; Drug: Venetoclax 50 MG Oral Tablet [Venclexta]; Drug: Venetoclax 100 MG Oral Tablet [Venclexta]

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruges, Belgium, 8000
    • A.Z. Sint Jan AV
  • Brussels, Belgium, 1070
    • Université Libre de Bruxelles - Hôpital Erasme
  • Haine-Saint-Paul, Belgium, 7100
    • Hopital Jolimont
  • Liège, Belgium, 4000
    • CHU de Liège
  • Yvoir, Belgium, 5530
    • Universite Catholique de Louvain Mont Godinne
• France
  • Angers, France, 49033
    • CHU d'Angers
  • Avignon, France, 84000
    • CH d'Avignon - Hopital Henri Duffaut
  • Bayonne, France, 64109
    • CH de la Côte Basque
  • Besançon, France, 25030
    • CHU Jean Minioz
  • Brest, France, 29609
    • CHU de Brest - Hopital de la Cavale Blanche
  • Caen, France, 14033
    • Institut d'Hématologie de Basse Normandie
  • Clermont-Ferrand, France, 63003
    • CHU Estaing
  • Créteil, France, 94010
    • CH Henri Mondor
  • Dijon, France, 21000
    • CHU de DIJON
  • La Roche-sur-Yon, France, 85925
    • CHD de Vendée
  • La Tronche, France, 38700
    • Chu de Grenoble
  • Lille, France, 59037
    • CHRU de Lille
  • Limoges, France, 87042
    • Hôpital Dupuytren
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13273
    • Institut Paoli Calmettes
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Nantes, France, 44093
    • Chu de Nantes
  • Paris, France, 75743
    • Hopital Necker
  • Paris, France, 75475
    • Hopital St-Louis
  • Pessac, France, 33604
    • Chu de Bordeaux - Hopital Haut-Leveque - Centre Francois Magendie
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • Hopital de la Milétrie
  • Pringy, France, 74374
    • CH Annecy Gennevois
  • Quimper, France, 29107
    • CH de Cornouaille
  • Reims, France, 51092
    • CHU de Reims
  • Rennes, France, 35033
    • Chu Pontchaillou
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint-Cloud, France, 92210
    • Hopital René Huguenin
  • Saint-Priest-en-Jarez, France, 42270
    • Institut de Cancérologie de la Loire Lucien Neuwirth
  • Strasbourg, France, 67033
    • Institut de cancérologie Strasbourg Europe
  • Toulouse, France, 31100
    • IUCT Oncopole
  • Tours, France, 37044
    • Chu Bretonneau
  • Vandœuvre-lès-Nancy, France, 54511
    • CHU Nancy Brabois
  • Vannes, France, 56017
    • CH de Bretagne Atlantique - Hopital Chubert
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospitals Nhs Foundation Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust
  • Plymouth, United Kingdom, PL6 8DH
    • University Hospitals Plymouth NHS Trust
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Ibrutinib (+ CD20Ab)	Drug: Ibrutinib 560 mg; 560mg/d continuously from C1D2 to end C24; Other Names: IMBRUVICA
Experimental: Arm B; Ibrutinib + Venetoclax (+CD20Ab)	Drug: Ibrutinib 560 mg; 560mg/d continuously from C1D2 to end C24; Other Names: IMBRUVICA; Drug: Venetoclax 10 MG Oral Tablet [Venclexta]; 20mg/d from C2D1 to C2D7; Other Names: Venclyxto 10 MG Oral Tablet; Drug: Venetoclax 50 MG Oral Tablet [Venclexta]; 50mg/d from C2D8 to C2D14; Other Names: Venclyxto 50 MG Oral Tablet; Drug: Venetoclax 100 MG Oral Tablet [Venclexta]; 100mg/d from C2D15 to C2D21 200mg/d from C2D22 to C2D28 400mg/d from C3D1 to end C24; Other Names: Venclyxto 100 MG Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum residual disease (MRD) rate	Minimum residual disease rate using droplet digital PCR (ddPCR) in bone marrow (BM) and/or peripheral blood (PB) at the end of induction	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRD rate	MRD response using quantified PCR (qPCR) in PB and BM	6 months
MRD rate	MRD response using ddPCR in PB and BM	12 months
MRD rate	MRD response using ddPCR in PB and BM	24 months
MRD rate	MRD response using ddPCR in PB	3 months
MRD rate	MRD response using ddPCR in PB	18 months
MRD rate	MRD response using ddPCR in PB	30 months
MRD rate	MRD response using ddPCR in PB	36 months
MRD rate	MRD response using ddPCR in PB	42 months
Overall response rate (ORR)	Overall response rate according to Lugano criteria	3 months
ORR	Overall response rate according to Lugano criteria	6 months
ORR	Overall response rate according to Lugano criteria	12 months
ORR	Overall response rate according to Lugano criteria	18 months
ORR	Overall response rate according to Lugano criteria	24 months
ORR	Overall response rate according to Lugano criteria	30 months
ORR	Overall response rate according to Lugano criteria	36 months
ORR	Overall response rate according to Lugano criteria	42 months
Complete response rate (CRR)	Complete response rate according to Lugano criteria	3 months
CRR	Complete response rate according to Lugano criteria	6 months
CRR	Complete response rate according to Lugano criteria	12 months
CRR	Complete response rate according to Lugano criteria	18 months
CRR	Complete response rate according to Lugano criteria	24 months
CRR	Complete response rate according to Lugano criteria	30 months
CRR	Complete response rate according to Lugano criteria	36 months
CRR	Complete response rate according to Lugano criteria	42 months
Progression free survival (PFS)	Progression free survival: time from randomization into the study to the first observation of documented clinical disease progression or death due to any cause	5,5 years
Overall survival (OS)	Overall survival from the date of randomization to the date of death from any cause	5,5 years
Duration of MRD negativity	time from the date of attainment the first negative MRD to the date of positive MRD	5,5 years
Delay from MRD positivity to clinical relapse	time from the date of attainment the first positive MRD based on PB or BM to the first observation of documented disease progression or death due to any cause	5,5 years
Duration of response	time from attainment of Complete Response (CR) or Partial Response (PR) to the date of first documented disease progression, relapse or death from any cause	5,5 years
Disease free survival	time from attainment of CR to the date of the first documented disease progression, relapse or death from any cause	5,5 years

Collaborators and Investigators

• Sponsor: The Lymphoma Academic Research Organisation
• Collaborators: Institute of Cancer Research, United Kingdom
• Investigators: Principal Investigator: Steven Le Gouill, Lymphoma Study Association; Principal Investigator: Toby Eyre, NCRI UK; Principal Investigator: David Lewis, NCRI UK

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): September 30, 2031

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Mantle-Cell; Pharmaceutical Preparations; Dosage Forms; venetoclax; Tablets; ibrutinib
• Other Study ID Numbers: OASIS-II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No