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

Sponsor
The Lymphoma Academic Research Organisation (Other)
Overall Status
Recruiting
CT.gov ID
NCT04802590
Collaborator
Institute of Cancer Research, United Kingdom (Other)
194
Enrollment
40
Locations
2
Arms
116.4
Anticipated Duration (Months)
4.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
  • 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

Study Type:
Interventional
Anticipated 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 :
Jan 18, 2022
Anticipated Primary Completion Date :
Mar 31, 2026
Anticipated Study Completion Date :
Sep 30, 2031

Arms and Interventions

ArmIntervention/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

Primary Outcome Measures

  1. Minimum residual disease (MRD) rate [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 [6 months]

    MRD response using quantified PCR (qPCR) in PB and BM

  2. MRD rate [12 months]

    MRD response using ddPCR in PB and BM

  3. MRD rate [24 months]

    MRD response using ddPCR in PB and BM

  4. MRD rate [3 months]

    MRD response using ddPCR in PB

  5. MRD rate [18 months]

    MRD response using ddPCR in PB

  6. MRD rate [30 months]

    MRD response using ddPCR in PB

  7. MRD rate [36 months]

    MRD response using ddPCR in PB

  8. MRD rate [42 months]

    MRD response using ddPCR in PB

  9. Overall response rate (ORR) [3 months]

    Overall response rate according to Lugano criteria

  10. ORR [6 months]

    Overall response rate according to Lugano criteria

  11. ORR [12 months]

    Overall response rate according to Lugano criteria

  12. ORR [18 months]

    Overall response rate according to Lugano criteria

  13. ORR [24 months]

    Overall response rate according to Lugano criteria

  14. ORR [30 months]

    Overall response rate according to Lugano criteria

  15. ORR [36 months]

    Overall response rate according to Lugano criteria

  16. ORR [42 months]

    Overall response rate according to Lugano criteria

  17. Complete response rate (CRR) [3 months]

    Complete response rate according to Lugano criteria

  18. CRR [6 months]

    Complete response rate according to Lugano criteria

  19. CRR [12 months]

    Complete response rate according to Lugano criteria

  20. CRR [18 months]

    Complete response rate according to Lugano criteria

  21. CRR [24 months]

    Complete response rate according to Lugano criteria

  22. CRR [30 months]

    Complete response rate according to Lugano criteria

  23. CRR [36 months]

    Complete response rate according to Lugano criteria

  24. CRR [42 months]

    Complete response rate according to Lugano criteria

  25. Progression free survival (PFS) [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) [5,5 years]

    Overall survival from the date of randomization to the date of death from any cause

  27. Duration of MRD negativity [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 [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 [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 [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

Criteria

Ages Eligible for Study:
18 Years to 79 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

  1. Stage II-IV disease, measurable with at least lymph node > 1.5 cm and requiring treatment in the opinion of the treating clinician

  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2.

  3. Life expectancy of more than 3 months.

  4. 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

  1. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study

  2. 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

  3. Pregnant, planning to become pregnant, or lactating woman

  4. Known hypersensitivity to study treatment (CD20 Ab, Ibrutinib, Venetoclax) or to any of the excipients

  5. Known allergy to xanthine oxidase inhibitors or rasburicase

  6. Known glucose-6-phosphate dehydrogenase (G6DP) deficiency

  7. Known bleeding disorders

  8. Severe prior reactions to monoclonal antibodies or with prior significant toxicity (other than thrombocytopenia) from Bcl-2 inhibitor

  9. 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

  1. Anti-cancer therapies including chemotherapy, radiotherapy or other investigational therapy, including targeted small molecule agents

  2. Biological agents (e.g. monoclonal antibodies) for anti-neoplastic intent: excluded 30 days prior to first dose of venetoclax

  3. Person deprived of his/her liberty by a judicial or administrative decision

  4. Adult person under legal protection

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1A.Z. Sint Jan AVBrugesBelgium8000
2Universite Libre de Bruxelles - Hopital ERASMEBrusselsBelgium1070
3Hopital JolimontHaine-Saint-PaulBelgium7100
4CHU de LiegeLiegeBelgium4000
5Universite Catholique de Louvain Mont GodinneYvoirBelgium5530
6CHU d'AngersAngersFrance49033
7CH d'Avignon - Hopital Henri DuffautAvignonFrance84000
8CH de la Côte BasqueBayonneFrance64109
9CHU Jean MiniozBesançonFrance25030
10Chu MorvanBrestFrance29609
11Institut d'Hématologie de Basse NormandieCaenFrance14033
12Chu EstaingClermont-FerrandFrance63003
13CH Henri MondorCréteilFrance94010
14CHU de DIJONDijonFrance21000
15CHD de VendéeLa Roche-sur-YonFrance85925
16CHU de GrenobleLa TroncheFrance38700
17CHRU de LilleLille CedexFrance59037
18Hopital DUPUYTRENLIMOGES CedexFrance87042
19Centre Léon BérardLYON Cedex 08France69373
20Institut Paoli CalmettesMarseille CedexFrance13273
21CHU de MontpellierMontpellierFrance34295
22CHU de NantesNantesFrance44093
23Hopital St-LouisParisFrance75475
24Hopital NECKERParisFrance75743
25Chu de Bordeaux - Hopital Haut-Leveque - Centre Francois MagendiePessacFrance33604
26Centre Hospitalier Lyon SudPierre Bénite CedexFrance69495
27Hopital de la MilétriePoitiersFrance86021
28Ch Annecy GennevoisPringyFrance74374
29CH de CornouailleQuimperFrance29107
30CHU de REIMSReimsFrance51092
31CHU PontchaillouRennesFrance35033
32Centre Henri BECQUERELRouenFrance76038
33Hopital René HugueninSaint Cloud CedexFrance92210
34Institut de Cancérologie de la Loire Lucien NeuwirthSaint-Priest-en-JarezFrance42270
35Institut de Cancérologie Strasbourg EuropeStrasbourgFrance67033
36IUCT OncopoleToulouseFrance31100
37CHU BretonneauToursFrance37044
38CHU Nancy BraboisVandœuvre-lès-NancyFrance54511
39CH de Bretagne Atlantique - Hopital CHUBERTVannesFrance56017
40Institut Gustave ROUSSYVILLEJUIF CedexFrance94805

Sponsors and Collaborators

  • The Lymphoma Academic Research Organisation
  • 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 Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT04802590
Other Study ID Numbers:
  • OASIS-II
First Posted:
Mar 17, 2021
Last Update Posted:
Mar 18, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 18, 2022