Clinical trial NCT04802590: Study of Ibrutinib + CD20 Antibody and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
Official title: A Randomized Phase II Trial Evaluating Ibrutinib Plus CD20 Ab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Institute of Cancer Research, United Kingdom
First posted: 2021-03-17
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Minimum residual disease (MRD) rate
timeFrame: 6 months
Secondary outcomes:
measure: MRD rate
timeFrame: 6 months
measure: MRD rate
timeFrame: 12 months
measure: MRD rate
timeFrame: 24 months
measure: MRD rate
timeFrame: 3 months
measure: MRD rate
timeFrame: 18 months
measure: MRD rate
timeFrame: 30 months
measure: MRD rate
timeFrame: 36 months
measure: MRD rate
timeFrame: 42 months
measure: Overall response rate (ORR)
timeFrame: 3 months
measure: ORR
timeFrame: 6 months
measure: ORR
timeFrame: 12 months
measure: ORR
timeFrame: 18 months
measure: ORR
timeFrame: 24 months
measure: ORR
timeFrame: 30 months
measure: ORR
timeFrame: 36 months
measure: ORR
timeFrame: 42 months
measure: Complete response rate (CRR)
timeFrame: 3 months
measure: CRR
timeFrame: 6 months
measure: CRR
timeFrame: 12 months
measure: CRR
timeFrame: 18 months
measure: CRR
timeFrame: 24 months
measure: CRR
timeFrame: 30 months
measure: CRR
timeFrame: 36 months
measure: CRR
timeFrame: 42 months
measure: Progression free survival (PFS)
timeFrame: 5,5 years
measure: Overall survival (OS)
timeFrame: 5,5 years
measure: Duration of MRD negativity
timeFrame: 5,5 years
measure: Delay from MRD positivity to clinical relapse
timeFrame: 5,5 years
measure: Duration of response
timeFrame: 5,5 years
measure: Disease free survival
timeFrame: 5,5 years
Other outcomes:
Locations:
city: Bruges
country: Belgium
facility: A.Z. Sint Jan AV
city: Brussels
country: Belgium
facility: Universite Libre de Bruxelles - Hopital ERASME
city: Haine-Saint-Paul
country: Belgium
facility: Hopital Jolimont
city: Liege
country: Belgium
facility: CHU de Liege
city: Yvoir
country: Belgium
facility: Universite Catholique de Louvain Mont Godinne
city: Angers
country: France
facility: CHU d'Angers
city: Avignon
country: France
facility: CH d'Avignon - Hopital Henri Duffaut
city: Bayonne
country: France
facility: CH de la Côte Basque
city: Besançon
country: France
facility: CHU Jean Minioz
city: Brest
country: France
facility: Chu Morvan
city: Caen
country: France
facility: Institut d'Hématologie de Basse Normandie
city: Clermont-Ferrand
country: France
facility: Chu Estaing
city: Créteil
country: France
facility: CH Henri Mondor
city: Dijon
country: France
facility: CHU de DIJON
city: La Roche-sur-Yon
country: France
facility: CHD de Vendée
city: La Tronche
country: France
facility: CHU de Grenoble
city: Lille Cedex
country: France
facility: CHRU de Lille
city: LIMOGES Cedex
country: France
facility: Hopital DUPUYTREN
city: LYON Cedex 08
country: France
facility: Centre Léon Bérard
city: Marseille Cedex
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hopital St-Louis
city: Paris
country: France
facility: Hopital NECKER
city: Pessac
country: France
facility: Chu de Bordeaux - Hopital Haut-Leveque - Centre Francois Magendie
city: Pierre Bénite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: Hopital de la Milétrie
city: Pringy
country: France
facility: Ch Annecy Gennevois
city: Quimper
country: France
facility: CH de Cornouaille
city: Reims
country: France
facility: CHU de REIMS
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: Centre Henri BECQUEREL
city: Saint Cloud Cedex
country: France
facility: Hopital René Huguenin
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire Lucien Neuwirth
city: Strasbourg
country: France
facility: Institut de Cancérologie Strasbourg Europe
city: Toulouse
country: France
facility: IUCT Oncopole
city: Tours
country: France
facility: CHU Bretonneau
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy Brabois
city: Vannes
country: France
facility: CH de Bretagne Atlantique - Hopital CHUBERT
city: VILLEJUIF Cedex
country: France
facility: Institut Gustave ROUSSY
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital Trust
Study officials:
affiliation: Lymphoma Study Association
name: Steven Le Gouill
role: PRINCIPAL_INVESTIGATOR
affiliation: NCRI UK
name: Toby Eyre
role: PRINCIPAL_INVESTIGATOR
affiliation: NCRI UK
name: David Lewis
role: PRINCIPAL_INVESTIGATOR
References: