OASIS II - A randomized phase II trial evaluating Ibrutinib plus CD20 Ab and Ibrutinib-Venetoclax plus CD20 Ab in patients with untreated mantle cell lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lysarc

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Immune System Diseases [C20]

Trial duration

5 Jan 2022 → ongoing

Decision date (initial)

2024-05-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512634-15-00

EudraCT number

2020-004910-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective is to estimate the minimum residual disease (MRD) rate using droplet digital PCR (ddPCR) in bone marrow and/or peripheral blood at the end of induction (after 6 cycles of Ibrutinib/CD20 Ab and Ibrutinib/CD20 Ab/Venetoclax) in previously untreated MCL patients.

Secondary objectives 12

1. MRD response in PB and BM at the following timepoints: o C6 (qPCR +/- NGS +/- any other technique recommended by state of art) o C12 (ddPCR +/- NGS +/- any other technique recommended by state of art) o C24 (ddPCR +/- NGS +/- any other technique recommended by state of art) o Permanent treatment discontinuation (due to progression/relapse)
2. MRD response in PB (ddPCR / NGS or any other technique recommended by state of art at the time of the analysis) at the following timepoints: C3 – C18 – C30 – C36 – C42
3. Overall response rate (Lugano response criteria 2014)
4. Complete response rate (Lugano response criteria 2014)
5. Overall Survival
6. Progression Free Survival
7. Response duration
8. Duration of MRD negativity and delay from MRD positivity to clinical relapse
9. Disease free survival
10. Tolerability and safety of Ibrutinib/CD20 Ab and Ibrutinib/CD20 Ab/Venetoclax
11. Investigate peripheral blood stem cell collection after at least 12 cycles and a washout period of 4 weeks for venetoclax
12. The key secondary objective is to evaluate the Progression Free Survival at 3 years from randomization to progression or death from any cause.

Conditions and MedDRA coding

Patients with untreated mantle cell lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 studyspecific 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 highly effective method of contraception (failure rate of less than 1%) during treatment and for eighteen months after the last drug administration.
6. Histologically confirmed (according to the 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 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 MDRD
9. Adequate hepatic function per local laboratory reference range as follow: o Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0 x upper limit of normal (ULN) o 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. 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 24

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., phenprocoumone)
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 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the MRD negativity rate at the end of induction (after 6 cycles) in the informative MRD set using ddPCR technique. We expect to have an increase of 12% of the MRD negativity rate in each arm.

Secondary endpoints 1

1. PFS at 3 years. We expect to have an increase of 10% of the PFS at 3 years in each arm.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lysarc

Sponsor organisation

LYSARC

Address

2d Lyon Sud Batiment

City

Pierre Benite Cedex

Postcode

69495

Country

France

Scientific contact point

Organisation

LYSARC

Contact name

Steven Le Gouill

Public contact point

Organisation

LYSARC

Contact name

Steven Le Gouill

Locations

2 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications