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

NCT04802590 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: OASIS-II
• Study Type: interventional
• Target: 194
• Locations: 3 countries
• Sites: 45

Brief 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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (30)

• MRD rate

  6 months

• MRD rate

  12 months

• MRD rate

  24 months

• MRD rate

  3 months

• MRD rate

  18 months

Study Arms (2)

Arm A

EXPERIMENTAL

Ibrutinib (+ CD20Ab)

Drug: Ibrutinib 560 mg

Arm B

EXPERIMENTAL

Ibrutinib + Venetoclax (+CD20Ab)

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]

Interventions

Ibrutinib 560 mg DRUG

560mg/d continuously from C1D2 to end C24

Also known as: IMBRUVICA

Arm A; Arm B

Venetoclax 10 MG Oral Tablet [Venclexta] DRUG

20mg/d from C2D1 to C2D7

Also known as: Venclyxto 10 MG Oral Tablet

Arm B

Venetoclax 50 MG Oral Tablet [Venclexta] DRUG

50mg/d from C2D8 to C2D14

Also known as: Venclyxto 50 MG Oral Tablet

Arm B

Venetoclax 100 MG Oral Tablet [Venclexta] DRUG

100mg/d from C2D15 to C2D21 200mg/d from C2D22 to C2D28 400mg/d from C3D1 to end C24

Also known as: Venclyxto 100 MG Oral Tablet

Arm B

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is ≥ 18 years and \< 80 years of age at the time of signing the informed consent form (ICF).
• Patient understood and voluntarily signed and dated an ICF prior to any study-specific assessments/procedures being conducted.
• Patient willing and able to adhere to the study visit schedule and other protocol requirements
• 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
• 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.
• 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)
• Untreated MCL
• 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)
• 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)
• Stage II-IV disease, measurable with at least lymph node \> 1.5 cm and requiring treatment in the opinion of the treating clinician
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.
• Life expectancy of more than 3 months.
• For France: patient affiliated to any social security system

You may not qualify if:

• 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.
• Impaired organ function (other than liver and renal) which will interfere with the treatment
• Hemoglobin level \< 10g/dL; Neutrophil count \<1 G/L; Platelets \< 75 G/L (except if related to lymphoma then platelet must be \>50),
• Major surgery within 28 days before enrollment
• Known central nervous system lymphoma
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)
• Requires treatment with strong CYP3A inhibitors
• Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine)
• Known history of human immunodeficiency virus (HIV)
• 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
• Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study
• 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

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Institute of Cancer Research, United Kingdom: collaborator

Study Sites (45)

A.Z. Sint Jan AV

Bruges, 8000, Belgium

Location

Universite Libre de Bruxelles - Hopital ERASME

Brussels, 1070, Belgium

Location

Hopital Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

CHU de Liege

Liège, 4000, Belgium

Location

Universite Catholique de Louvain Mont Godinne

Yvoir, 5530, Belgium

Location

CHU d'Angers

Angers, 49033, France

Location

CH d'Avignon - Hopital Henri Duffaut

Avignon, 84000, France

Location

CH de la Côte Basque

Bayonne, 64109, France

Location

CHU Jean Minioz

Besançon, 25030, France

Location

Chu de Brest - Hopital de La Cavale Blanche

Brest, 29609, France

Location

Institut d'Hématologie de Basse Normandie

Caen, 14033, France

Location

Chu Estaing

Clermont-Ferrand, 63003, France

Location

CH Henri Mondor

Créteil, 94010, France

Location

CHU de DIJON

Dijon, 21000, France

Location

CHD de Vendée

La Roche-sur-Yon, 85925, France

Location

CHU de Grenoble

La Tronche, 38700, France

Location

CHRU de Lille

Lille, 59037, France

Location

Hopital DUPUYTREN

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CHU de Montpellier

Montpellier, 34295, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hopital St-Louis

Paris, 75475, France

Location

Hopital NECKER

Paris, 75743, France

Location

Chu de Bordeaux - Hopital Haut-Leveque - Centre Francois Magendie

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Hopital de la Milétrie

Poitiers, 86021, France

Location

Ch Annecy Gennevois

Pringy, 74374, France

Location

CH de Cornouaille

Quimper, 29107, France

Location

CHU de REIMS

Reims, 51092, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Centre Henri BECQUEREL

Rouen, 76038, France

Location

Hopital René Huguenin

Saint-Cloud, 92210, France

Location

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Institut de Cancérologie Strasbourg Europe

Strasbourg, 67033, France

Location

IUCT Oncopole

Toulouse, 31100, France

Location

CHU Bretonneau

Tours, 37044, France

Location

CHU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

CH de Bretagne Atlantique - Hopital CHUBERT

Vannes, 56017, France

Location

Institut Gustave ROUSSY

Villejuif, 94805, France

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, NR4 7UY, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, PL6 8DH, United Kingdom

Location

Royal Cornwall Hospital Trust

Truro, TR1 3LJ, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; venetoclax; Tablets

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Steven Le Gouill

  Lymphoma Study Association

  PRINCIPAL INVESTIGATOR

• Toby Eyre

  NCRI UK

  PRINCIPAL INVESTIGATOR

• David Lewis

  NCRI UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 17, 2021
• Study Start: January 24, 2022
• Primary Completion: March 31, 2026
• Study Completion (Estimated): September 30, 2031
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (35); BE (5); GB (5)