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

March 16, 2023 updated by: The Lymphoma Academic Research Organisation

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

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

194

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Bruges, Belgium, 8000
        • Recruiting
        • A.Z. Sint Jan AV
        • Contact:
        • Principal Investigator:
          • Sylvia SNAUWAERT, Dr
      • Brussels, Belgium, 1070
        • Recruiting
        • Université Libre de Bruxelles - Hôpital Erasme
        • Contact:
        • Principal Investigator:
          • Virginie DE WILDE, Pr
      • Haine-Saint-Paul, Belgium, 7100
        • Recruiting
        • Hopital Jolimont
        • Contact:
        • Principal Investigator:
          • Marie-Christine NGIRABACU, Dr
      • Liege, Belgium, 4000
        • Recruiting
        • CHU de Liège
        • Contact:
        • Principal Investigator:
          • Christophe BONNET, Dr
      • Yvoir, Belgium, 5530
        • Recruiting
        • Université Catholique de Louvain Mont Godinne
        • Contact:
        • Principal Investigator:
          • Marc ANDRE, Dr
  • France
      • Angers, France, 49033
        • Recruiting
        • CHU d'Angers
        • Contact:
        • Principal Investigator:
          • Marie-Pierre MOLES-MOREAU, Dr
      • Avignon, France, 84000
        • Recruiting
        • CH d'Avignon - Hopital Henri Duffaut
        • Contact:
        • Principal Investigator:
          • Hacene ZERAZHI, Dr
      • Bayonne, France, 64109
        • Recruiting
        • CH de la Côte Basque
        • Contact:
        • Principal Investigator:
          • Anne BANOS, Dr
      • Besançon, France, 25030
        • Recruiting
        • CHU Jean Minioz
        • Contact:
        • Principal Investigator:
          • Adrien CHAUCHET, Dr
      • Brest, France, 29609
        • Recruiting
        • CHU Morvan
        • Contact:
        • Principal Investigator:
          • Adrian TEMPESCUL, Dr
      • Caen, France, 14033
        • Recruiting
        • Institut d'Hématologie de Basse Normandie
        • Contact:
        • Principal Investigator:
          • Gandhi DAMAJ, Dr
      • Clermont-Ferrand, France, 63003
        • Recruiting
        • CHU Estaing
        • Contact:
        • Principal Investigator:
          • Victoria CACHEUX, Dr
      • Créteil, France, 94010
        • Recruiting
        • CH Henri Mondor
        • Contact:
        • Principal Investigator:
          • Jehan DUPUIS, Dr
      • Dijon, France, 21000
        • Recruiting
        • CHU de Dijon
        • Contact:
        • Principal Investigator:
          • Olivier CASASNOVAS, Dr
      • LIMOGES Cedex, France, 87042
        • Recruiting
        • Hôpital Dupuytren
        • Contact:
        • Principal Investigator:
          • Julie ABRAHAM, Dr
      • LYON Cedex 08, France, 69373
        • Recruiting
        • Centre LEON BERARD
        • Contact:
        • Principal Investigator:
          • Emmanuelle NICOLAS-VIRELIZIER, Dr
      • La Roche-sur-Yon, France, 85925
        • Recruiting
        • CHD de Vendée
        • Contact:
        • Principal Investigator:
          • Nadine MORINEAU, Dr
      • La Tronche, France, 38700
        • Recruiting
        • CHU de Grenoble
        • Contact:
        • Principal Investigator:
          • Rémy GRESSIN, Dr
      • Lille Cedex, France, 59037
        • Recruiting
        • CHRU de Lille
        • Contact:
        • Principal Investigator:
          • Franck MORSCHHAUSER, Pr
      • Marseille Cedex, France, 13273
        • Recruiting
        • Institut Paoli Calmettes
        • Contact:
        • Principal Investigator:
          • Jean-Marc SCHIANO DE COLELLA, Dr
      • Montpellier, France, 34295
        • Recruiting
        • CHU de Montpellier
        • Contact:
        • Principal Investigator:
          • Guillaume CARTRON, Dr
      • Nantes, France, 44093
        • Recruiting
        • CHU de Nantes
        • Contact:
        • Principal Investigator:
          • Steven LE GOUILL, Pr
      • Paris, France, 75743
        • Recruiting
        • Hopital Necker
        • Contact:
        • Principal Investigator:
          • David SIBON, Dr
      • Paris, France, 75475
        • Recruiting
        • Hopital St-Louis
        • Contact:
        • Principal Investigator:
          • Catherine THIEBLEMONT, Pr
      • Pessac, France, 33604
        • Recruiting
        • Chu de Bordeaux - Hopital Haut-Leveque - Centre Francois Magendie
        • Contact:
        • Principal Investigator:
          • Kamal BOUABDALLAH, Dr
      • Pierre Bénite Cedex, France, 69495
        • Recruiting
        • Centre Hospitalier Lyon Sud
        • Contact:
        • Principal Investigator:
          • SAFAR VIOLAINE, Dr
      • Poitiers, France, 86021
        • Recruiting
        • Hôpital de la Milétrie
        • Contact:
        • Principal Investigator:
          • Vincent DELWAIL, Dr
      • Pringy, France, 74374
        • Recruiting
        • Ch Annecy Gennevois
        • Contact:
        • Principal Investigator:
          • Nicolas DAGUINDAU, Dr
      • Quimper, France, 29107
        • Recruiting
        • CH de Cornouaille
        • Contact:
        • Principal Investigator:
          • Ronan LE CALLOCH, Dr
      • Reims, France, 51092
        • Recruiting
        • CHU de Reims
        • Contact:
        • Principal Investigator:
          • Eric DUROT, Dr
      • Rennes, France, 35033
        • Recruiting
        • CHU Pontchaillou
        • Contact:
        • Principal Investigator:
          • Thierry LAMY DE LA CHAPELLE, Pr
      • Rouen, France, 76038
        • Recruiting
        • Centre Henri Becquerel
        • Contact:
        • Principal Investigator:
          • Hervé TILLY, Pr
      • Saint Cloud Cedex, France, 92210
        • Recruiting
        • Hôpital René Huguenin
        • Contact:
        • Principal Investigator:
          • Carole SOUSSAIN, Dr
      • Saint-Priest-en-Jarez, France, 42270
        • Recruiting
        • Institut de Cancérologie de la Loire Lucien Neuwirth
        • Contact:
        • Principal Investigator:
          • Ludovic FOUILLET, Dr
      • Strasbourg, France, 67033
        • Recruiting
        • Institut de cancerologie Strasbourg Europe
        • Contact:
        • Principal Investigator:
          • Luc-Matthieu FORNECKER, Pr
      • Toulouse, France, 31100
        • Recruiting
        • IUCT Oncopole
        • Contact:
        • Principal Investigator:
          • Lucie OBERIC, Dr
      • Tours, France, 37044
        • Recruiting
        • CHU Bretonneau
        • Contact:
        • Principal Investigator:
          • Laurianne DRIEU LA ROCHELLE, Dr
      • VILLEJUIF Cedex, France, 94805
        • Recruiting
        • Institut Gustave Roussy
        • Contact:
        • Principal Investigator:
          • Vincent RIBRAG, Dr
      • Vandœuvre-lès-Nancy, France, 54511
        • Recruiting
        • CHU Nancy Brabois
        • Contact:
        • Principal Investigator:
          • Pierre FEUGIER, Pr
      • Vannes, France, 56017
        • Recruiting
        • CH de Bretagne Atlantique - Hopital Chubert
        • Contact:
        • Principal Investigator:
          • Antoine BONNET, Dr
  • United Kingdom
      • Manchester, United Kingdom, M20 4BX
      • Norwich, United Kingdom, NR4 7UY
        • Recruiting
        • Norfolk and Norwich University Hospitals NHS Foundation Trust
        • Principal Investigator:
          • Nimish Shah
        • Contact:
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Oxford University Hospitals NHS Foundation Trust
        • Principal Investigator:
          • Toby Eyre
        • Contact:
      • Plymouth, United Kingdom, PL6 8DH
        • Recruiting
        • University Hospitals Plymouth NHS Trust
        • Principal Investigator:
          • David Lewis
        • Contact:
      • Truro, United Kingdom, TR1 3LJ
        • Recruiting
        • Royal Cornwall Hospital Trust
        • Contact:
        • Principal Investigator:
          • Michelle Furtado

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Experimental: Arm B
Ibrutinib + Venetoclax (+CD20Ab)
Drug: Ibrutinib 560 mg
560mg/d continuously from C1D2 to end C24
Drug: Venetoclax 10 MG Oral Tablet [Venclexta]
20mg/d from C2D1 to C2D7
Drug: Venetoclax 50 MG Oral Tablet [Venclexta]
50mg/d from C2D8 to C2D14
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum residual disease (MRD) rate
Time Frame: 6 months
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
Time Frame: 6 months
MRD response using quantified PCR (qPCR) in PB and BM
6 months
MRD rate
Time Frame: 12 months
MRD response using ddPCR in PB and BM
12 months
MRD rate
Time Frame: 24 months
MRD response using ddPCR in PB and BM
24 months
MRD rate
Time Frame: 3 months
MRD response using ddPCR in PB
3 months
MRD rate
Time Frame: 18 months
MRD response using ddPCR in PB
18 months
MRD rate
Time Frame: 30 months
MRD response using ddPCR in PB
30 months
MRD rate
Time Frame: 36 months
MRD response using ddPCR in PB
36 months
MRD rate
Time Frame: 42 months
MRD response using ddPCR in PB
42 months
Overall response rate (ORR)
Time Frame: 3 months
Overall response rate according to Lugano criteria
3 months
ORR
Time Frame: 6 months
Overall response rate according to Lugano criteria
6 months
ORR
Time Frame: 12 months
Overall response rate according to Lugano criteria
12 months
ORR
Time Frame: 18 months
Overall response rate according to Lugano criteria
18 months
ORR
Time Frame: 24 months
Overall response rate according to Lugano criteria
24 months
ORR
Time Frame: 30 months
Overall response rate according to Lugano criteria
30 months
ORR
Time Frame: 36 months
Overall response rate according to Lugano criteria
36 months
ORR
Time Frame: 42 months
Overall response rate according to Lugano criteria
42 months
Complete response rate (CRR)
Time Frame: 3 months
Complete response rate according to Lugano criteria
3 months
CRR
Time Frame: 6 months
Complete response rate according to Lugano criteria
6 months
CRR
Time Frame: 12 months
Complete response rate according to Lugano criteria
12 months
CRR
Time Frame: 18 months
Complete response rate according to Lugano criteria
18 months
CRR
Time Frame: 24 months
Complete response rate according to Lugano criteria
24 months
CRR
Time Frame: 30 months
Complete response rate according to Lugano criteria
30 months
CRR
Time Frame: 36 months
Complete response rate according to Lugano criteria
36 months
CRR
Time Frame: 42 months
Complete response rate according to Lugano criteria
42 months
Progression free survival (PFS)
Time Frame: 5,5 years
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)
Time Frame: 5,5 years
Overall survival from the date of randomization to the date of death from any cause
5,5 years
Duration of MRD negativity
Time Frame: 5,5 years
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 Frame: 5,5 years
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 Frame: 5,5 years
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 Frame: 5,5 years
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

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 24, 2022

Primary Completion (Anticipated)

March 31, 2026

Study Completion (Anticipated)

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)

March 17, 2023

Last Update Submitted That Met QC Criteria

March 16, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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