REtreatment with VEnetoclax and Acalabrutinib after venetoclax Limited duration (REVEAL) 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)

Phase 2

Recruiting

• Conditions: chronic lymphocytic leukemia; CLL; 10024324

• Registration Number: NL-OMON52450
• Lead Sponsor: HOVO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 49

Inclusion Criteria

• Documented CLL or SLL requiring treatment according to IWCLL criteria 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), 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);
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

Exclusion Criteria

• 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);
• Severe pulmonary dysfunction (CTCAE grade III-IV);
• Severe neurological or psychiatric disease (CTCAE grade III-IV);
• 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 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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• uMRD in BM by flow cytometry after 26 cycles (2 acalabrutinib and 24 AV).</p><br>