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CLL/SLLPhase 1/2AETHERNCT05791409

Venetoclax Treatment (26 Cycles) With 6 Cycles or 12 Cycles of Epcoritamab in Patients With Relapsed or Refractory CLL or SLL

A Phase 1/2 study testing Epcoritamab and Venetoclax in people with CLL/SLL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 29 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

In this study, efficacy and safety of 2 regimens that combine the CD3-CD20 T cell engager epcoritamab with venetoclax will be tested in relapsed/refractory CLL and SLL patients. The trial starts with phase I part to establish the recommended dose level (RDL) of epcoritamab in the combination with venetoclax for the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
CLL/SLL
What is being tested?
Epcoritamab and Venetoclax
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
29 sitesin 5 countries
Study dates
15 Apr 2024to Dec 2032
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented relapsed or refractory CLL or SLL (SLL in phase II part only) following at least one systemic 1st-line treatment
  • Requiring treatment according to IWCLL criteria (appendix A);
  • Age at least 18 years;
  • ECOG/WHO performance status 0-2;
  • In case of prior venetoclax treatment, enrollment can only occur at least 24 months after end of treatment and patients must not have progressed during venetoclax treatment;
  • Adequate BM function defined as:
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  • Hemoglobin >5.6 mmol/l or Hb > 9 g/dL, unless low Hb is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
  • Absolute neutrophil count (ANC) >1.0 x 109/L (1,000/μL), unless low ANC is directly attributable to CLL infiltration of the BM, proven by BM biopsy;
  • Platelet count >30 x 109/L (30,000/μL), unless low platelets is directly attributable to CLL infiltration in the BM;
  • Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl) ≥ 50ml/min (Cockcroft-Gault appendix F);
  • Adequate liver function as indicated:
  • Serum aspartate transaminase (ASAT) and alanine transaminase (ALAT) ≤ 3.0 x upper limit of normal (ULN);
  • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or controlled autoimmune hemolytic anemia);
  • Prothrombin time (PT)/International normal ratio (INR) <1.5x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN; unless receiving anticoagulation;
  • Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded; Please note: For patients positive for anti-HBc, HBV-DNA PCR has to be repeated every month until 12 months after last dose of study treatment.
  • Patient is able and willing to adhere to the study visit schedule and other protocol requirements;
  • Patient is capable of giving informed consent;
  • Written informed consent.

Who cannot join

  • Active CLL/SLL directed therapy within the last 14 days;
  • Prior treatment with a CD3 × CD20 bispecific antibody or CAR T-cell therapy
  • Transformation of CLL (Richter's transformation);
  • Prior allogeneic stem cell transplantation and/or solid organ transplantation;
  • Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML);
  • Malignancies other than CLL currently requiring systemic therapy or not treated in curative intention or showing signs of progression after curative treatment;
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  • Known allergy to xanthine oxidase inhibitors and/or rasburicase;
  • History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components);
  • Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease);
  • Active fungal, bacterial, and/or viral infection CTCAEgrade > 1; Please note: active controlled as well as chronic/recurrent infections are at risk of reactivation/infection during treatment;
  • Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, auto-immune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.);
  • Patient known to be HIV-positive;
  • Patient requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor/inducer (see appendix J) or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists;
  • CTCAE grade III-IV cardiovascular disease including but not limited to:
  • Unstable or uncontrolled disease/condition related to or affecting cardiac function, eg, unstable angina, congestive heart failure grade III or IV as classified by the New York Heart Association (see appendix E), uncontrolled clinically significant cardiac arrhythmia (CTCAE grade II or higher), or clinically significant electrocardiogram (ECG) abnormalities.
  • Myocardial infarction, intracranial bleed, or stroke within the past 6 months.
  • Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >480 msec. NOTE: this criterion does not apply to subjects with a left bundle branch block.
  • Stroke or intracranial hemorrhage within 6 months prior to registration.
  • Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);
  • Severe neurological or psychiatric disease (CTCAE grade III-IV, see appendix D);
  • Neuropathy > CTCAE grade II
  • Patient who has difficulty with or are unable to swallow oral medication, or have significant gastrointestinal disease that would limit absorption of oral medication;
  • Vaccination with live vaccines within 28 days prior to registration;
  • Use of any other experimental drug or therapy within 28 days of registration;
  • Major surgery within 28 days prior to registration;
  • Pregnant women and nursing mothers;
  • Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device, sexual abstinence or combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) during study treatment and for 12 months after last dose of epcoritamab and 30 days after last dose of venetoclax;
  • Previous participation in the HOVON 139 CLL or HOVON 140 CLL trial and eligible for and willing to participate in the HOVON 159 CLL trial;
  • Current participation in other clinical trial with medicinal products;
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Trial locations and contacts

29 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Mark-David Levin contact

m-d.levin@asz.nl

29 sites in 5 countries

Netherlands12 sites, 11 recruiting
  • NL-Den Bosch-JBZ

    's-Hertogenbosch

    Recruiting
  • NL-Alkmaar-NWZ

    Alkmaar

    Withdrawn
  • NL-Amersfoort-MEANDERMC

    Amersfoort

    Recruiting
  • NL-Amsterdam-AMC

    Amsterdam

    Recruiting
  • NL-Dordrecht-ASZ

    Dordrecht

    Recruiting
  • NL-Ede-ZGV

    Ede

    Recruiting
  • NL-Eindhoven-CATHARINA

    Eindhoven

    Recruiting
  • NL-Groningen-UMCG

    Groningen

    Recruiting
  • NL-Leeuwarden-MCL

    Leeuwarden

    Recruiting
  • NL-Den Haag-HAGA

    The Hague

    Recruiting
  • NL-Tilburg-ETZ

    Tilburg

    Recruiting
  • NL-Utrecht-UMCUTRECHT

    Utrecht

    Recruiting

Other trials in Netherlands

Germany9 sites, 7 recruiting
  • DE-Berlin-HELIOSBERLINBUCH

    Berlin

    Withdrawn
  • DE-Köln-UKKOELN

    Cologne

    Recruiting
  • DE-Freiburg-UNIKLINIKFREIBURG

    Freiburg im Breisgau

    Recruiting
  • DE-Greifswald-UNIGREIFSWALD

    Greifswald

    Withdrawn
  • DE-Halle-UMH

    Halle

    Recruiting
  • DE-Kiel-UKSH

    Kiel

    Recruiting
  • DE-Munster-GEMEINSCHAFTSPRAXIS

    Münster

    Recruiting
  • DE-Stuttgart-RBK

    Stuttgart

    Recruiting
  • DE-Ulm-UNIKLINKULM

    Ulm

    Recruiting

Other trials in Germany

Australia3 sites, 3 recruiting
  • AU-Melbourne-ALFRED

    Melbourne

    Recruiting
  • AU-Melbourne-MONASH

    Melbourne

    Recruiting
  • AU-Melbourne-SVHM

    Melbourne

    Recruiting

Other trials in Australia

Denmark3 sites, 2 recruiting
  • DK-Aalborg-ALBOGUH

    Aalborg

    Withdrawn
  • DK-Copenhagen-RIGSHOSPITALET

    Copenhagen

    Recruiting
  • DK-Odense-OUH

    Odense

    Recruiting

Other trials in Denmark

Belgium2 sites, 2 recruiting
  • BE-Antwerpen-ZNASTUIVENBERG

    Antwerp

    Recruiting
  • BE-Roeselare-AZDELTA

    Roeselare

    Recruiting

Other trials in Belgium

About this study

Official title: A Prospective Randomized Phase I/II Trial of Venetoclax Treatment (26 Cycles) With 6 Cycles or 12 Cycles of Epcoritamab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

In this study, efficacy and safety of 2 regimens that combine the CD3-CD20 T cell engager epcoritamab with venetoclax will be tested in relapsed/refractory CLL and SLL patients. The trial starts with phase I part to establish the recommended dose level (RDL) of epcoritamab in the combination with venetoclax for the phase II trial.

Conditions
CLL/SLL
Being tested
Epcoritamab, Venetoclax

What participants receive

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

  • EpcoritamabDrug

    Number of cycles of epcoritamab is either 6 (cycle 1-6) or 12 (cycle 1-12). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

  • VenetoclaxDrug

    All patients will receive venetoclax cycle 1-26 (a 5 week ramp-up of venetoclax will precede the first cycle). Patients will be treated until they have received the total number of assigned treatment cycles or until progression, or severe toxicity, whichever comes first.

Study groups in NCT05791409
Study groupRoleWhat they receive
Arm AExperimental6 cycles epcoritamab + 26 cycles venetoclax
Receives: Drug: Epcoritamab; Drug: Venetoclax
Arm BExperimental12 cycles epcoritamab + 26 cycles venetoclax
Receives: Drug: Epcoritamab; Drug: Venetoclax

What is being measured

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

  1. • Recommended phase II dose (RP2D) for the combination of venetoclax and epcoritamab based on dose limiting toxicity (DLT)

    endpoint for phase I and both arms

    Measured: 6-12 months

  2. • Undetectable minimal residual disease <10-4 (uMRD) in BM in absence of progression according to IWCLL criteria at 12 weeks after cycle 26

    endpoint for phase II and both arms

    Measured: 29 months

Secondary outcomes (14)
  1. • Minimal residual disease (MRD) status in PB at cycle 4, 6, 9, 12, 15, 18, 21, 24 and 12 weeks after cycle 26; following treatment: every 3 months for the first year, then every 6 months until relapse or until 6 years after registration

    both arms

    Measured: 6 years

  2. • Progression free survival (PFS), defined as time from registration to the first occurrence of disease progression or death from any cause, whichever occurs first.

    both arms

    Measured: 6 years

  3. Overall survival (OS), defined as the time from registration to death from any cause.

    both arms

    Measured: 6 years

  4. Best overall response rate (ORR) defined as the proportion of patients with a complete response (CR), complete response with incomplete marrow recovery (CRi), or partial response (PR) according to IWCLL 2018 criteria.

    both arms

    Measured: 6 years

  5. • Event free survival (EFS), defined as time from randomization to date start of next CLL treatment, progression or death, whichever comes first.

    both arms

    Measured: 6 years

  6. • Time to next CLL treatment (TTNT), defined as time from randomization to next new line of treatment.

    both arms

    Measured: 6 years

  7. • Treatment free survival (TFS), defined as time from date of last protocol treatment to date start of next (new) line of treatment, or death from any cause, whichever comes first.

    both arms

    Measured: 6 years

  8. Duration of response (DOR), defined as time from first response (i.e., ≥PR and CR) to PD or death from any cause.

    both arms

    Measured: 6 years

  9. • Depth (level) of minimal residual disease (MRD) measured in BM after cycle 9 and 12 weeks after cycle 26.

    both arms

    Measured: 29 months

  10. • Depth (level) of minimal residual disease measured in PB at cycle 4, 6, 9, 12, 15, 18, 21, 24, 12 weeks after cycle 26 and thereafter every 3 months for the first year, then every 6 months until relapse or until 6 years after registration

    both arms

    Measured: 6 years

  11. Safety parameters: Type, frequency, and severity of- adverse events (AEs) and- adverse events of special interest (AESI) and their relationship to study treatment (determined according to CTCAE v5.0).

    both arms

    Measured: 6 years

  12. Health-related quality of life (QoL) by EORTC QLQ-C30 questionnaires.

    both arms

    Measured: 6 years

  13. Health-related quality of life (QoL) by QLQ-CLL17 questionnaires.

    both arms

    Measured: 6 years

  14. Health-related quality of life (QoL) by PRO-CTCAE questionnaires.

    both arms

    Measured: 6 years

Timeline

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

  1. First posted30 Mar 2023
  2. Study start15 Apr 2024
  3. Primary completionMar 2029 (estimated)
  4. Study completionDec 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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
112 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05791409
Sponsor's protocol ID
HO165 CLL
Acronym
AETHER
Status last verified
Sep 2026
First submitted
1 Feb 2023
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Epcoritamab and Venetoclax in people with CLL/SLL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 29 sites in 5 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 18 inclusion and 30 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: looking for participants now, as of the sponsor's last update on 5 Oct 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 Netherlands, Germany, Australia, Denmark, 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 Arnon Kater (+31 6-11491753, a.p.kater@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

• Recommended phase II dose (RP2D) for the combination of venetoclax and epcoritamab based on dose limiting toxicity (DLT) (time frame: 6-12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 5 Oct 2026.

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