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

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ClinicalTrials.gov Identifier: NCT04802590
Recruitment Status : Recruiting
First Posted : March 17, 2021
Last Update Posted : March 18, 2022
Sponsor:
Collaborator:
Institute of Cancer Research, United Kingdom
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation

Study Description
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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.


Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma 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] Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 194 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial Evaluating Ibrutinib Plus CD20 Ab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma
Actual Study Start Date : January 18, 2022
Estimated Primary Completion Date : March 31, 2026
Estimated Study Completion Date : September 30, 2031

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. MRD rate [ Time Frame: 6 months ]
    MRD response using quantified PCR (qPCR) in PB and BM

  2. MRD rate [ Time Frame: 12 months ]
    MRD response using ddPCR in PB and BM

  3. MRD rate [ Time Frame: 24 months ]
    MRD response using ddPCR in PB and BM

  4. MRD rate [ Time Frame: 3 months ]
    MRD response using ddPCR in PB

  5. MRD rate [ Time Frame: 18 months ]
    MRD response using ddPCR in PB

  6. MRD rate [ Time Frame: 30 months ]
    MRD response using ddPCR in PB

  7. MRD rate [ Time Frame: 36 months ]
    MRD response using ddPCR in PB

  8. MRD rate [ Time Frame: 42 months ]
    MRD response using ddPCR in PB

  9. Overall response rate (ORR) [ Time Frame: 3 months ]
    Overall response rate according to Lugano criteria

  10. ORR [ Time Frame: 6 months ]
    Overall response rate according to Lugano criteria

  11. ORR [ Time Frame: 12 months ]
    Overall response rate according to Lugano criteria

  12. ORR [ Time Frame: 18 months ]
    Overall response rate according to Lugano criteria

  13. ORR [ Time Frame: 24 months ]
    Overall response rate according to Lugano criteria

  14. ORR [ Time Frame: 30 months ]
    Overall response rate according to Lugano criteria

  15. ORR [ Time Frame: 36 months ]
    Overall response rate according to Lugano criteria

  16. ORR [ Time Frame: 42 months ]
    Overall response rate according to Lugano criteria

  17. Complete response rate (CRR) [ Time Frame: 3 months ]
    Complete response rate according to Lugano criteria

  18. CRR [ Time Frame: 6 months ]
    Complete response rate according to Lugano criteria

  19. CRR [ Time Frame: 12 months ]
    Complete response rate according to Lugano criteria

  20. CRR [ Time Frame: 18 months ]
    Complete response rate according to Lugano criteria

  21. CRR [ Time Frame: 24 months ]
    Complete response rate according to Lugano criteria

  22. CRR [ Time Frame: 30 months ]
    Complete response rate according to Lugano criteria

  23. CRR [ Time Frame: 36 months ]
    Complete response rate according to Lugano criteria

  24. CRR [ Time Frame: 42 months ]
    Complete response rate according to Lugano criteria

  25. 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

  26. Overall survival (OS) [ Time Frame: 5,5 years ]
    Overall survival from the date of randomization to the date of death from any cause

  27. 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

  28. 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

  29. 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

  30. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04802590


Contacts
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Contact: Anne FAUGIER +33 (0)4 87 91 57 13 anne.faugier@lysarc.org

Locations
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Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Institute of Cancer Research, United Kingdom
Investigators
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Principal Investigator: Steven Le Gouill Lymphoma Study Association
Principal Investigator: Toby Eyre NCRI UK
Principal Investigator: David Lewis NCRI UK
More Information
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Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT04802590    
Other Study ID Numbers: OASIS-II
First Posted: March 17, 2021    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Venetoclax
Antineoplastic Agents