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Chronic Lymphocytic LeukemiaPhase 2EVITANCT07738887

Epcoritamab Plus Venetoclax Plus Ibrutinib in Patients With Chronic Lymphocytic Leukemia With TP53 Alterations

A Phase 2 study testing Ibrutinib Oral Tablet, Venetoclax Oral Tablet and Epcoritamab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by The Lymphoma Academic Research Organisation at 29 sites in 2 countries.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a phase 2, open-label, multicenter study evaluating the efficacy and safety of a fixed-duration combination of epcoritamab, venetoclax, and ibrutinib (EVI) in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have TP53 alterations. Read more about this study

Who is it for?
Ages 18 to 79 years
What is being tested?
Ibrutinib Oral Tablet, Venetoclax Oral Tablet and Epcoritamab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
29 sitesin 2 countries
Study dates
31 Dec 2026to 30 Jun 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant who understood and voluntarily signed and dated an informed consent form prior to any trial-specific assessments/procedures being conducted
  • Must be able to adhere to the trial visit schedule and other protocol requirements
  • Age between ≥ 18 years and < 80 years at the time of signing the informed consent form (ICF)
  • Cumulative Illness Rating Score (CIRS) ≤ 6
  • CD20+, untreated and documented CLL or SLL, with a Royal Marsden Hospital (RMH) or Matutes Score > 3. For SLL a detectable clone with a CLL phenotype in the peripheral blood is a prerequisite for trial participation.
  • Presence of TP53 abnormalities (either 17p deletion by FISH and/or TP53 mutations) according to ERIC recommandations.17
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  • Participant requiring treatment according to 2018 iwCLL guidelines 18
  • Presence of measurable disease (absolute lymphocyte count > 5,000/μL, palpable or measurable lymph node ≥1.5cm on imaging, or bone marrow involvement
  • ECOG performance status 0 to 2
  • Adequate hematopoietic function within 7 days before the participant's enrollment
  • ANC ≥ 1 G/L
  • And Platelets ≥ 50 G/L
  • And Hemoglobin ≥ 8 g/dL
  • Note: Platelets and/or red blood cells transfusions may be administered during screening to meet this requirement
  • Adequate renal function defined by a Creatinine Clearance ≥ 50 ml/min calculated according to MDRD or CKD-EPI or Cockcroft-Gault (using actual body weight).
  • Adequate liver function, as indicated by a total bilirubin <1.5 x ULN, AST and ALT <3 x ULN value, unless directly attributed to the participant's CLL/SLL or to Gilbert's Syndrome (the ULN is based on institutional values)
  • The participant must have been vaccinated against pneumococcal (< 5 years) and SARS-CoV-2 (< 1 year) with at least 21 days between the last vaccination and the participant's enrollment
  • Woman of childbearing potential (WOCBP):
  • should have a negative result for pregnancy test (minimum sensitivity of 25 mIU/mL, urine or serum), within 28 days prior the participant's enrollment
  • should agree to use 1 form of highly effective method of contraception from the time of screening until at least 12 months after the final dose of epcoritamab, or at least 3 months after the final dose of ibrutinib or at least 30 days after the final dose of venetoclax, whichever is the longest
  • Woman should agree to abstain from breastfeeding during trial participation and at least 4 months after the last study treatment administration
  • Woman should agree to perform further pregnancy testing monthly
  • Woman should agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial, until 12 months after the last administration of study treatment.
  • Man of reproductive potential should agree to use an acceptable method of birth control during treatment and until at least 12 months after the final dose of epcoritamab, 3 months after the final dose of ibrutinib and 30 days after the final dose of venetoclax (see section 15.7.3 Acceptable birth control methods). Men should agree not to donate sperm during the entire trial and until 12 months after the last administration of study treatment.
  • Participant covered by any social security system (France)
  • Participant who understands and speaks one of the country official languages unless local regulation authorizes independent translators
  • Life expectancy > 6 months

Who cannot join

  • Any prior CLL or SLL-specific therapies, even including rituximab used for autoimmune cytopenias.
  • Clinically significant cardiovascular disease including the following:
  • Myocardial infarction within 6 months prior to ICF signature
  • Unstable angina within 3 months prior to ICF signature
  • NYHA class III or IV heart failure
  • Uncontrolled hypertension
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  • History of clinically significant arrhythmias (including sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes).
  • QTcF > 480 msec using the Fridericia formula
  • History of Mobitz II second- or third-degree heart block without permanent pacemaker
  • LVEF <50% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan
  • Child-Pugh liver cirrhosis.
  • Clinical evidence for Central Nervous System involvement by CLL
  • History of ongoing or confirmed Progressive Multifocal Leukoencephalopathy (PML).
  • Active autoimmune disease or other disease requiring permanent immunosuppressive treatment including steroids therapy > 20mg daily of prednisone dose or equivalent within 15 days prior participant's enrollment
  • Active, uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent within 15 days prior participant's enrollment
  • Any prior history of Richter transformation or DLBCL
  • Active malignancy other than the one treated in this trial. Prior history of malignancies unless the participant has been free of the disease for ≥ 2 years.
  • However, participants with the following history /conditions that have been treated with a curative intent are allowed:
  • Non-invasive basal cell or epidermoid carcinoma (non melanoma)
  • In situ carcinoma of the cervix
  • In situ carcinoma of the breast
  • Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis [TNM] clinical staging system Woman with adjuvant endocrine therapy (I.e., hormonotherapy) after breast cancer treatment can be enrolled if hormonotherapy was started for ≥ 2 years
  • History of stroke or intracranial hemorrhage within 6 months prior to ICF signature.
  • Major surgery anticipated before the ICF signature
  • Known bleeding disorders
  • Active Hepatitis C Virus (HCV) infection (RNA PCR-positive). Participants who received treatment for HCV infection that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable
  • Active Hepatitis B Virus (HBV) infection (DNA PCR-positive). Participants with evidence of prior HBV infection but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy during the entire treatment with active monitoring of viral load in the blood
  • Known history of seropositivity for HIV infection
  • Known or suspected hypersensitivity or anaphylaxis to trial intervention(s) including active substance or to any of the excipients.
  • Requires treatment with warfarin, other vitamin K antagonists, or dual antiplatelet therapy
  • Requires treatment with a strong cytochrome CYP3A4 inhibitor/inducer
  • Vaccinated with live, attenuated vaccines within 6 months of enrollment
  • Participation in another clinical study who would compromise the participation to the current study.
  • Use of any standard or experimental anti-cancer drug therapy within 28 days or 5 half-lives (whichever is shorter) before the participant's enrollment
  • Any prior therapy with a bispecific antibody targeting CD3 and CD20
  • Prior allogeneic stem cells or autologous transplant.
  • Pregnant, planning to become pregnant or lactating woman
  • Any significant medical conditions, or laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical trial (according to the investigator's decision)
  • Ongoing active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the first dose of trial drug, including COVID-19 infection and participants with positive cytomegalovirus PCR.
  • Participant deprived of their liberty by a judicial or administrative decision
  • Participant hospitalized without consent
  • Adult participant under legal protection

Trial locations and contacts

29 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Project management contact

+33 4 72 66 93 33

evita@lysarc.org

29 sites in 2 countries

France24 sites

  • CHU d'ANGERS

    Angers, 49100

    ALINE CLAVERT, +33241354472, ALINE.CLAVERT@CHU-ANGERS.FR

    Aline CLAVERT, doctor

  • Institut D'Hematologie de Basse Normandie

    Caen, 14000

    Baptiste DELAPIERRE, +33231272124, delapierre-ba@chu-caen.fr

    Baptiste DELAPIERRE, doctor

  • Ch Metropole Savoie

    Chambéry, 73000

    PIERRE FAURIE, +33479965650, PIERRE.FAURIE@CH-METROPOLE-SAVOIE.FR

    PIERRE FAURIE, doctor

  • Chu Estaing

    Clermont-Ferrand, 63100

    Romain Guieze, +33675463972, rguieze@chu-clermontferrand.fr

    Romain Guieze, Professor

  • Chd de Vendee

    La Roche-sur-Yon, 85000

    Jessie Bourcier, +33251446173, jessie.bourcier@ght85.fr

    Jessie Bourcier, doctor

  • Ch Du Mans-Centre de Cancerologie de La Sarthe

    Le Mans, 72100

    Kamel LARIBI, +33243434361, KLARIBI@CH-LEMANS.FR

    Kamel LARIBI, doctor

  • Chu de Lille - Hopital Claude Huriez

    Lille, 59000

    Ines ARIB, +33320444290, ines.arib@chu-lille.fr

    Ines ARIB, doctor

  • Chu Lyon-Sud

    Lyon, 69310

    EMMANUELLE FERRANT, +33478864521, EMMANUELLE.FERRANT2@CHU-LYON.FR

    EMMANUELLE FERRANT, doctor

  • Institut Paoli Calmettes

    Marseille, 13009

    Anne CALLEJA, +33491223866, callejaa@ipc.unicancer.fr

    Anne CALLEJA, doctor

  • Chr Metz-Thionville - Hopital de Mercy

    Metz, 57530

    Philippe Carassou, +33610902135, p.carassou@chr-metz-thionville.fr

    Philippe Carassou, doctor

  • Ch Mont-de-Marsan - Hopital de Layné

    Mont-de-Marsan, 40000

    Lea GREUB, +33558051160, lea.greub@ch-mdm.fr

    Lea GREUB, doctor

  • CHU DE Montpellier

    Montpellier, 34090

    Emmanuelle Tchernonog, +33467336733, e-tchernonog@chu-montpellier.fr

    Emmanuelle Tchernonog, doctor

  • Chu de Nantes

    Nantes, 44000

    Chloé ANTIER, +33240083271, chloe.antier@chu-nantes.fr

    Chloé ANTIER, doctor

  • Centre Antoine Lacassagne

    Nice, 06100

    LUCA INCHIAPPA, +3328285633, LUCA.INCHIAPPA@NICE.UNICANCER.FR

    LUCA INCHIAPPA, Doctor

  • AP-HP Saint-Louis

    Paris, 75010

    Agathe Vely, +33142499236, agathe.vely@aphp.fr

    Agathe Vely, doctor

  • AP-HP Pitié Salpêtrière

    Paris, 75013

    DAMIEN ROOSWEIL, +33142161529, DAMIEN.ROOSWEIL@APHP.FR

    DAMIEN ROOSWEIL, doctor

  • Gustave Roussy Cancer Campus Grand Paris

    Paris, 94800

    David Ghez, +33142114321, david.ghez@gustaveroussy.fr

    David Ghez, doctor

  • CHU de Bordeaux HOPITAL HAUT-LEVEQUE

    Pessac, 33000

    Raphaelle Aubrais, +33557656511, raphaelle.aubrais@chu-bordeaux.fr

    raphaelle aubrais, doctor

  • Chu de Poitiers - Hopital de La Miletrie

    Poitiers, 86000

    Cecile Tomowiak, cecile.tomowiak@chu-poitiers.fr

    +33549444689

  • Ch Rene Dubos

    Pontoise, 95300

    Sinziana Ioana SARGHI, +33130754040, sinziana-ioana.sarghi@ght-novo.fr

    Sinziana Ioana SARGHI, Doctor

  • Chu Pontchaillou

    Rennes, 35000

    Sophie De Guibert, +33299284291, sophie.de.guibert@chu-rennes.fr

    Sophie De Guibert, Doctor

  • Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne

    Saint-Etienne, 42270

    Valentin Daguerre, +33477822856, Valentin.daguerre@chu-st-etienne.fr

    Valentin Daguerre, Doctor

  • Chru de Strasbourg

    Strasbourg, 67000

    Luc matthieu Fornecker, +33368766767, luc-matthieu.fornecker@chru-strasbourg.fr

    Luc matthieu Fornecker, Profesor

  • Iuct Oncopole

    Toulouse, 31100

    Loic Ysabaert, +33531156351, YSEBAERT.LOIC@IUCT-ONCOPOLE.FR

    Loic Ysabaert, Profesor

Other trials in France

Belgium5 sites

  • Institut Jules Bordet

    Brussels, 1070

    Virginie Dewilde, +3225555097, virginie.dewilde@hubruxelles.be

    Virginie Dewilde, Doctor

  • Universitair Ziekenhuis Gent

    Ghent, 9000

    Willem Daneels, +3293322125, willem.daneels@uzgent.be

    Willem Daneels, Doctor

  • HELORA - Hôpital de La Louvière Site Jolimont

    La Louvière, 7100

    Marie Christine Ngirabacu, +3264235071, marie-christine.ngirabacu@helora.be

    Marie Christine Ngirabacu, doctor

  • U.Z. LEUVEN - Campus GASTHUISBERG

    Leuven, 3001

    Ann Janssens, +3216346880, ann.janssens@uzleuven.be

    Ann Janssens, Doctor

  • Chu Ucl Namur - Site Godinne

    Namur, 5000

    Bernard WIVINE, +3281423844, wivine.bernard@chuuclnamur.uclouvain.be

    Bernard WIVINE, Doctor

Other trials in Belgium

About this study

This is a phase 2, open-label, multicenter study evaluating the efficacy and safety of a fixed-duration combination of epcoritamab, venetoclax, and ibrutinib (EVI) in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have TP53 alterations.

Patients with TP53 abnormalities, including TP53 mutation and/or 17p deletion, have a poorer prognosis and are less likely to benefit from conventional chemoimmunotherapy. Targeted therapies such as ibrutinib and venetoclax have improved outcomes in this population, but many patients eventually experience disease progression. This study investigates whether adding epcoritamab, a CD3×CD20 bispecific antibody, to the combination of ibrutinib and venetoclax can improve the depth and durability of treatment responses while using a fixed-duration treatment approach.

Participants will receive sequential treatment with ibrutinib alone, followed by ibrutinib plus venetoclax, and then the triple combination of epcoritamab, venetoclax, and ibrutinib. The study will evaluate the effectiveness of this regimen, including the achievement of deep remission, as well as its safety and tolerability in this high-risk patient population.

Being tested
Ibrutinib Oral Tablet, Venetoclax Oral Tablet, Epcoritamab
Keywords
CLL, SLL, TP53 mutation
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ibrutinib Oral TabletDrug

    Also called IMBRUVICA

    Orally once daily, administered alone during the initial treatment phase and continued in combination with venetoclax and epcoritamab according to the study treatment schedule.

  • Venetoclax Oral TabletDrug

    Oral administration as part of the study treatment regimen, in combination with ibrutinib and subsequently with epcoritamab according to the study treatment schedule.

  • EpcoritamabDrug

    Subcutaneous administration as part of the study treatment regimen in combination with ibrutinib and venetoclax according to the study treatment schedule

Study groups in NCT07738887
Study groupRoleWhat they receive
EVI combinationExperimentalParticipants receive sequential treatment with ibrutinib, followed by ibrutinib plus venetoclax, and subsequently the triple combination of ibrutinib, venetoclax, and epcoritamab as a fixed-duration treatment regimen.
Receives: Drug: Ibrutinib Oral Tablet; Drug: Venetoclax Oral Tablet; Drug: Epcoritamab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Participants Achieving Complete Remission (CR) with Undetectable Minimal Residual Disease (uMRD) in Bone Marrow

    Rate of participants achieving complete remission (CR) with undetectable minimal residual disease (uMRD) in bone marrow, assessed according to 2018 iwCLL response criteria.

    Measured: 18 months

Secondary outcomes (10)

  1. Bone Marrow uMRD Rate

    Proportion of participants with undetectable minimal residual disease in bone marrow.

    Measured: 18 months

  2. Complete Response Rate (CRR)

    Proportion of participants achieving complete response according to iwCLL 2018 criteria.

    Measured: 18 months

  3. Overall Response Rate (ORR)

    Proportion of participants achieving complete or partial response according to iwCLL 2018 criteria.

    Measured: 18 months

  4. Duration of Response

    Time from first response to disease progression or death

    Measured: 4 years

  5. Duration of Complete Response

    Time from complete response to relapse or progression

    Measured: 4 years

  6. Time to Next Treatment

    Time from treatment initiation to start of next anti-CLL therapy.

    Measured: 4 years

  7. Peripheral Blood MRD Kinetics

    Assessment of MRD dynamics in peripheral blood during and after treatment

    Measured: Day 1 of Cycle7 (each cycle is 28 days); 18 months; Follow-up Months12; Follow-up Months 24

  8. Progression-Free Survival (PFS)

    Time from treatment initiation to disease progression or death

    Measured: 3 years

  9. Overall Survival (OS)

    Time from treatment initiation to death from any cause

    Measured: 3 years

  10. Safety and tolerability (Adverse Events)

    Incidence and severity of adverse events including serious adverse events and immune-related toxicities

    Measured: 38 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2026
  2. Study start31 Dec 2026 (estimated)
  3. Primary completion31 Dec 2029 (estimated)
  4. Study completion30 Jun 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07738887
Sponsor's protocol ID
EVITA
Other IDs
2025-520893-20-00, 2025
Acronym
EVITA
Status last verified
Jul 2026
First submitted
27 Jul 2026
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib Oral Tablet, Venetoclax Oral Tablet and Epcoritamab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by The Lymphoma Academic Research Organisation at 29 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in France, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Project management (+33 4 72 66 93 33, evita@lysarc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Participants Achieving Complete Remission (CR) with Undetectable Minimal Residual Disease (uMRD) in Bone Marrow (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07738887.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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