CLL/SLLPhase 2NCT04523428
REtreatment With VEnetoclax and Acalabrutinib After Venetoclax Limited Duration (REVEAL)
A Phase 2 study testing Venetoclax/Acalabrutinib in people with CLL/SLL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 18 sites in 3 countries.
Trial summary
Fixed-duration regimens containing combinations of venetoclax with CD20 targeting agents are expected to soon become standard practice in first-line patients with chronic lymfocytic leukemia (CLL). 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?
- Venetoclax/Acalabrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 18 sitesin 3 countries
- Study dates
- 23 Dec 2020to Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented CLL or SLL requiring treatment according to IWCLL criteria (appendix A) after at least (clinical) partial response as best response after the following initial study treatment: venetoclax-rituximab in HOVON 140/GAIA or venetoclax-obinutuzumab in HOVON 139/GIVE or HOVON 140/GAIA;
- WHO/ECOG performance status 0-3 (appendix C), stage 3 only if attributable to CLL
- Age at least 18 years;
- Adequate BM function defined as:
- Hemoglobin >5 mmol/l or Hb > 8 g/dL
- Absolute neutrophil count (ANC) >0.75 x 109/L (750/μL), unless directly attributable to CLL infiltration of the BM, proven by BM biopsy
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- Platelet count >30 x 109/L (30,000/μL) without transfusion and irrespective whether it is attributable to CLL infiltration in the BM;
- Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl ≥ 30ml/min (Cockcroft-Gault appendix E); Please note: in case eGFR or CrCl is <50ml/min the patient needs to be considered high risk for TLS
- 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 of nonhepatic origin);
- Prothrombin time (PT)/International normal ratio (INR) <1.5 x ULN and activated partial thromboplastin time (aPTT) <1.5 x ULN;
- 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). Subjects 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
- Any prior therapy with BTK inhibitor;
- Prior treatment with venetoclax other than first line;
- Other therapy with exception of chemo-/immunotherapy which is allowed also after venetoclax first line relapse;
- Transformation of CLL (Richter's transformation);
- 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 history of bleeding diathesis (e.g. hemophilia or von Willebrand disease);
- Active fungal, bacterial, and/or viral infection that requires systemic therapy; 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; Please note: Patients being treated with DOACs apixaban, edoxaban or rivaroxaban can be included, but must be properly informed about the potential risk of bleeding under treatment with acalabrutinib. (see appendix J)
- History of stroke or intracranial hemorrhage within 6 months prior to registration;
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease, myocardial infarction within 6 months) (CTCAE grade III-IV, see appendix D);
- Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);
- Severe neurological or psychiatric disease (CTCAE grade III-IV, see appendix D);
- 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;
- Steroid therapy within 10 days prior to registration, with the exception of inhaled steroids for asthma, topical steroids, steroids up to 20 mg or dose equivalents of prednisolone daily to control autoimmune phenomenon's, or replacement/stress corticosteroids;
- 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 30 days after end of treatment;
- Current participation in other clinical trial (other than follow up HOVON139/HOVON140);
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Trial locations and contacts
18 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
18 sites in 3 countries
Netherlands15 sites, 15 recruiting
- Recruiting
NL-Den Bosch-JBZ
's-Hertogenbosch
- Recruiting
NL-Amsterdam-AMC
Amsterdam
- Recruiting
NL-Arnhem-RIJNSTATE
Arnhem
- Recruiting
NL-Breda-AMPHIA
Breda
- Recruiting
NL-Delft-RDGG
Delft
- Recruiting
NL-Dordrecht-ASZ
Dordrecht
- Recruiting
NL-Ede-ZGV
Ede
- Recruiting
NL-Eindhoven-MAXIMAMC
Eindhoven
- Recruiting
NL-Groningen-UMCG
Groningen
- Recruiting
NL-Leeuwarden-MCL
Leeuwarden
- Recruiting
NL-Maastricht-MUMC
Maastricht
- Recruiting
NL-Nieuwegein-ANTONIUS
Nieuwegein
- Recruiting
NL-Rotterdam-IKAZIA
Rotterdam
- Recruiting
NL-Rotterdam-MAASSTADZIEKENHUIS
Rotterdam
- Recruiting
NL-Utrecht-UMCUTRECHT
Utrecht
Belgium2 sites, 2 recruiting
- Recruiting
BE-Bruxelles-STLUC
Brussels
- Recruiting
BE-Leuven-UZLEUVEN
Leuven
About this study
Official title: A Prospective, Multicenter, Phase-II Trial of Venetoclax Plus Acalabrutinib in Patients Who Have Relapsed After First Line Venetoclax + Anti-CD20 mAb Treatment for Chronic Lymphocytic Leukemia (CLL or SLL)
Fixed-duration regimens containing combinations of venetoclax with CD20 targeting agents are expected to soon become standard practice in first-line patients with chronic lymfocytic leukemia (CLL). The advantage of a fixed duration venetoclax combination as part of first-line treatment is the potential to retreat with venetoclax in patients who develop relapsed disease after a treatment free period. However, efficacy of venetoclax retreatment following a fixed duration venetoclax combination is still hypothetical as clinical data are lacking. Thus, there is an urgent need for data proving efficacy of venetoclax combinations following venetoclax treatment cessation. Testing of a novel venetoclax-containing regimen for relapsed CLL without the repeat of anti-CD20 monoclonal antibody (mAb) is a rational approach.
Read the detailed description
First-line venetoclax and CD20 antibody containing regimens that are currently being tested are based on either a fixed duration schedule or on an MRD-based time-limited schedule. The assumption of these regimens is that, aside from the deep (often uMRD) and often longstanding remissions, relapsed disease can be retreated with a venetoclax-based regimen. This, however, has not been formally proven.
In this study, patients who received a first line regimen with either venetoclax and rituximab (GAIA/CLL13/HOVON 140 trial, [NCT02950051] ) or venetoclax and the second generation anti-CD20 antibody obinutuzumab (GAIA/CLL13/HOVON 140 trial, and the HOVON139 trial [Netherlands Trial Registry ID number #NTR6043]) and have relapsed with the need for a subsequent treatment are eligible to enter the study and to receive a combination of venetoclax with the highly selective BTK inhibitor acalabrutinib. Combination of venetoclax with acalabrutinib is expected to lead to uMRD, making discontinuation of therapy possible.
- Conditions
- CLL/SLL
- Being tested
- Venetoclax/Acalabrutinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venetoclax/AcalabrutinibDrug
Also called Venclexta, Venclyxto
All patients will receive a lead-in with 2 cycles of acalabrutinib 100 mg bid. Hereafter patients will continue with ramp-up of venetoclax followed by daily 400 mg venetoclax in combination with acalabrutinib for 24 cycles. Patients will be treated until they have received a total of 26 cycles or until progression, whichever comes first.
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax/Acalabrutinib | Experimental | All patients will receive a lead-in with 2 cycles of acalabrutinib 100 mg bid. Hereafter patients will continue with ramp-up of venetoclax followed by daily 400 mg venetoclax in combination with acalabrutinib for 24 cycles. Patients will be treated until they have received a total of 26 cycles or until progression, whichever comes first. Receives: Drug: Venetoclax/Acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
uMRD in BM by flow cytometry after 26 cycles (2 acalabrutinib and 24 AV).
To evaluate efficacy of acalabrutinib/venetoclax (AV) in terms of undetectable minimal residual disease (uMRD) response in bone marrow (BM) after 26 cycles of treatment in patients with CLL previously treated with venetoclax and anti-CD20 mAb.
Measured: 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start23 Dec 2020
- Primary completionDec 2028 (estimated)
- Study completionDec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CLL/SLLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen Nederland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- A. Kater, Principal investigator, AMC/HOVON
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04523428
- Sponsor's protocol ID
- HO159
- Status last verified
- Sep 2026
- First submitted
- 19 Aug 2020
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Phase-II Trial of Venetoclax Plus Acalabrutinib in Patients Who Have Relapsed After First Line Venetoclax + Anti-CD20 mAb Treatment for Chronic Lymphocytic Leukemia (CLL or SLL)
- ClinicalTrials.gov ID
- NCT04523428
- Acronym / sponsor ID
- HO159
- Conditions
- CLL/SLL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen NederlandUniversity, hospital or other
- Study start
- 23 Dec 2020 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2032 (estimated)
- First posted
- 21 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fixed-duration regimens containing combinations of venetoclax with CD20 targeting agents are expected to soon become standard practice in first-line patients with chronic lymfocytic leukemia (CLL). The advantage of a fixed duration venetoclax combination as part of first-line treatment is the potential to retreat with venetoclax in patients who develop relapsed disease after a treatment free period. However, efficacy of venetoclax retreatment following a fixed duration venetoclax combination is still hypothetical as clinical data are lacking. Thus, there is an urgent need for data proving efficacy of venetoclax combinations following venetoclax treatment cessation. Testing of a novel venetoclax-containing regimen for relapsed CLL without the repeat of anti-CD20 monoclonal antibody (mAb) is a rational approach.
Detailed description
First-line venetoclax and CD20 antibody containing regimens that are currently being tested are based on either a fixed duration schedule or on an MRD-based time-limited schedule. The assumption of these regimens is that, aside from the deep (often uMRD) and often longstanding remissions, relapsed disease can be retreated with a venetoclax-based regimen. This, however, has not been formally proven.
In this study, patients who received a first line regimen with either venetoclax and rituximab (GAIA/CLL13/HOVON 140 trial, [NCT02950051] ) or venetoclax and the second generation anti-CD20 antibody obinutuzumab (GAIA/CLL13/HOVON 140 trial, and the HOVON139 trial [Netherlands Trial Registry ID number #NTR6043]) and have relapsed with the need for a subsequent treatment are eligible to enter the study and to receive a combination of venetoclax with the highly selective BTK inhibitor acalabrutinib. Combination of venetoclax with acalabrutinib is expected to lead to uMRD, making discontinuation of therapy possible.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax/Acalabrutinib | Experimental | Drug: Venetoclax/AcalabrutinibAll patients will receive a lead-in with 2 cycles of acalabrutinib 100 mg bid. Hereafter patients will continue with ramp-up of venetoclax followed by daily 400 mg venetoclax in combination with acalabrutinib for 24 cycles. Patients will be treated until they have received a total of 26 cycles or until progression, whichever comes first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Documented CLL or SLL requiring treatment according to IWCLL criteria (appendix A) after at least (clinical) partial response as best response after the following initial study treatment: venetoclax-rituximab in HOVON 140/GAIA or venetoclax-obinutuzumab in HOVON 139/GIVE or HOVON 140/GAIA;
- WHO/ECOG performance status 0-3 (appendix C), stage 3 only if attributable to CLL
- Age at least 18 years;
- Adequate BM function defined as:
- Estimated Glomerular Filtration Rate (eGFR) (MDRD) or estimated creatinine clearance (CrCl ≥ 30ml/min (Cockcroft-Gault appendix E); Please note: in case eGFR or CrCl is <50ml/min the patient needs to be considered high risk for TLS
Key exclusion criteria (26 listed)
- Any prior therapy with BTK inhibitor;
- Prior treatment with venetoclax other than first line;
- Other therapy with exception of chemo-/immunotherapy which is allowed also after venetoclax first line relapse;
- Transformation of CLL (Richter's transformation);
- Patient with a history of confirmed progressive multifocal leukoencephalopathy (PML);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Venetoclax/AcalabrutinibAlso: Venclexta, VenclyxtoAll patients will receive a lead-in with 2 cycles of acalabrutinib 100 mg bid. Hereafter patients will continue with ramp-up of venetoclax followed by daily 400 mg venetoclax in combination with acalabrutinib for 24 cycles. Patients will be treated until they have received a total of 26 cycles or until progression, whichever comes first. | Drug | Venetoclax/Acalabrutinib |
Primary outcome
uMRD in BM by flow cytometry after 26 cycles (2 acalabrutinib and 24 AV).
Time frame: 26 months
To evaluate efficacy of acalabrutinib/venetoclax (AV) in terms of undetectable minimal residual disease (uMRD) response in bone marrow (BM) after 26 cycles of treatment in patients with CLL previously treated with venetoclax and anti-CD20 mAb.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Website of the HOVON organisationLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for CLL/SLL
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Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
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Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic
RecruitingPhase 1
A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia
Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
A. Kater principal investigator
AMC/HOVON
18 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Venetoclax/Acalabrutinib in people with CLL/SLL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 18 sites in 3 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 16 inclusion and 26 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 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Netherlands, Belgium, Denmark. 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 A. Kater (+31 20 5665785, 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?
uMRD in BM by flow cytometry after 26 cycles (2 acalabrutinib and 24 AV). (time frame: 26 months). 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 21 Sep 2026.