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

Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04802590
• Other study ID #: OASIS-II
• Status: Recruiting
• Phase: Phase 2
• Start date: January 24, 2022
• Est. completion date: September 30, 2031

Study information

• Verified date: March 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: Anne FAUGIER
• Phone: +33 (0)4 87 91 57 13
• Email: anne.faugier[@]lysarc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 194
• Est. completion date: September 30, 2031
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• Ibrutinib 560 mg
560mg/d continuously from C1D2 to end C24
• Venetoclax 10 MG Oral Tablet [Venclexta]
20mg/d from C2D1 to C2D7
• Venetoclax 50 MG Oral Tablet [Venclexta]
50mg/d from C2D8 to C2D14
• 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

Locations

Country	Name	City	State
Belgium	A.Z. Sint Jan AV	Bruges
Belgium	Universite Libre de Bruxelles - Hopital ERASME	Brussels
Belgium	Hopital Jolimont	Haine-Saint-Paul
Belgium	CHU de Liege	Liege
Belgium	Universite Catholique de Louvain Mont Godinne	Yvoir
France	CHU d'Angers	Angers
France	CH d'Avignon - Hopital Henri Duffaut	Avignon
France	CH de la Côte Basque	Bayonne
France	CHU Jean Minioz	Besançon
France	Chu Morvan	Brest
France	Institut d'Hématologie de Basse Normandie	Caen
France	Chu Estaing	Clermont-Ferrand
France	CH Henri Mondor	Créteil
France	CHU de DIJON	Dijon
France	CHD de Vendée	La Roche-sur-Yon
France	CHU de Grenoble	La Tronche
France	CHRU de Lille	Lille Cedex
France	Hopital DUPUYTREN	LIMOGES Cedex
France	Centre Léon Bérard	LYON Cedex 08
France	Institut Paoli Calmettes	Marseille Cedex
France	CHU de Montpellier	Montpellier
France	CHU de Nantes	Nantes
France	Hopital NECKER	Paris
France	Hopital St-Louis	Paris
France	Chu de Bordeaux - Hopital Haut-Leveque - Centre Francois Magendie	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite Cedex
France	Hopital de la Milétrie	Poitiers
France	Ch Annecy Gennevois	Pringy
France	CH de Cornouaille	Quimper
France	CHU de REIMS	Reims
France	CHU Pontchaillou	Rennes
France	Centre Henri BECQUEREL	Rouen
France	Hopital René Huguenin	Saint Cloud Cedex
France	Institut de Cancérologie de la Loire Lucien Neuwirth	Saint-Priest-en-Jarez
France	Institut de Cancérologie Strasbourg Europe	Strasbourg
France	IUCT Oncopole	Toulouse
France	CHU Bretonneau	Tours
France	CHU Nancy Brabois	Vandœuvre-lès-Nancy
France	CH de Bretagne Atlantique - Hopital CHUBERT	Vannes
France	Institut Gustave ROUSSY	VILLEJUIF Cedex
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Norfolk and Norwich University Hospitals NHS Foundation Trust	Norwich
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	University Hospitals Plymouth NHS Trust	Plymouth
United Kingdom	Royal Cornwall Hospital Trust	Truro

Sponsors (2)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation	Institute of Cancer Research, United Kingdom

Countries where clinical trial is conducted

Belgium,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	MRD rate	MRD response using quantified PCR (qPCR) in PB and BM	6 months
Secondary	MRD rate	MRD response using ddPCR in PB and BM	12 months
Secondary	MRD rate	MRD response using ddPCR in PB and BM	24 months
Secondary	MRD rate	MRD response using ddPCR in PB	3 months
Secondary	MRD rate	MRD response using ddPCR in PB	18 months
Secondary	MRD rate	MRD response using ddPCR in PB	30 months
Secondary	MRD rate	MRD response using ddPCR in PB	36 months
Secondary	MRD rate	MRD response using ddPCR in PB	42 months
Secondary	Overall response rate (ORR)	Overall response rate according to Lugano criteria	3 months
Secondary	ORR	Overall response rate according to Lugano criteria	6 months
Secondary	ORR	Overall response rate according to Lugano criteria	12 months
Secondary	ORR	Overall response rate according to Lugano criteria	18 months
Secondary	ORR	Overall response rate according to Lugano criteria	24 months
Secondary	ORR	Overall response rate according to Lugano criteria	30 months
Secondary	ORR	Overall response rate according to Lugano criteria	36 months
Secondary	ORR	Overall response rate according to Lugano criteria	42 months
Secondary	Complete response rate (CRR)	Complete response rate according to Lugano criteria	3 months
Secondary	CRR	Complete response rate according to Lugano criteria	6 months
Secondary	CRR	Complete response rate according to Lugano criteria	12 months
Secondary	CRR	Complete response rate according to Lugano criteria	18 months
Secondary	CRR	Complete response rate according to Lugano criteria	24 months
Secondary	CRR	Complete response rate according to Lugano criteria	30 months
Secondary	CRR	Complete response rate according to Lugano criteria	36 months
Secondary	CRR	Complete response rate according to Lugano criteria	42 months
Secondary	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
Secondary	Overall survival (OS)	Overall survival from the date of randomization to the date of death from any cause	5,5 years
Secondary	Duration of MRD negativity	time from the date of attainment the first negative MRD to the date of positive MRD	5,5 years
Secondary	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
Secondary	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
Secondary	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