REtreatment With VEnetoclax and Acalabrutinib After Venetoclax Limited Duration (REVEAL)

NCT04523428 | Recruiting Phase 2 DMC

• 1 other identifier: HO159
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 18

Brief 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). 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.

Conditions

CLL/SLL

Outcome Measures

Primary Outcomes (1)

• 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.

  26 months

Study Arms (1)

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.

Drug: Venetoclax/Acalabrutinib

Interventions

Venetoclax/Acalabrutinib DRUG

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.

Also known as: Venclexta, Venclyxto

Venetoclax/Acalabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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;

You may not qualify if:

• 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;
• 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);

Sponsors & Collaborators

• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead

Study Sites (18)

BE-Bruxelles-STLUC

Brussels, Belgium

RECRUITING

BE-Leuven-UZLEUVEN

Leuven, Belgium

RECRUITING

DK-Aarhus N-AUH

Aarhus, Denmark

RECRUITING

NL-Den Bosch-JBZ

's-Hertogenbosch, Netherlands

RECRUITING

NL-Amsterdam-AMC

Amsterdam, Netherlands

RECRUITING

NL-Arnhem-RIJNSTATE

Arnhem, Netherlands

RECRUITING

NL-Breda-AMPHIA

Breda, Netherlands

RECRUITING

NL-Delft-RDGG

Delft, Netherlands

RECRUITING

NL-Dordrecht-ASZ

Dordrecht, Netherlands

RECRUITING

NL-Ede-ZGV

Ede, Netherlands

RECRUITING

NL-Eindhoven-MAXIMAMC

Eindhoven, Netherlands

RECRUITING

NL-Groningen-UMCG

Groningen, Netherlands

RECRUITING

NL-Leeuwarden-MCL

Leeuwarden, Netherlands

RECRUITING

NL-Maastricht-MUMC

Maastricht, Netherlands

RECRUITING

NL-Nieuwegein-ANTONIUS

Nieuwegein, Netherlands

RECRUITING

NL-Rotterdam-IKAZIA

Rotterdam, Netherlands

RECRUITING

NL-Rotterdam-MAASSTADZIEKENHUIS

Rotterdam, Netherlands

RECRUITING

NL-Utrecht-UMCUTRECHT

Utrecht, Netherlands

RECRUITING

Related Links

• Website of the HOVON organisation

MeSH Terms

Interventions

venetoclax; acalabrutinib

Study Officials

• A. Kater

  AMC/HOVON

  PRINCIPAL INVESTIGATOR

Central Study Contacts

A. Kater

CONTACT

+31 20 5665785; a.p.kater@amsterdamumc.nl

H. Visser

CONTACT

+31 10 7041560; hovon@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 21, 2020
• Study Start: December 23, 2020
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2032
• Last Updated: January 6, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (15); BE (2); DK (1)