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.
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;
Hemoglobin >5 mmol/l or Hb > 8 g/dL
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);
Single group
Venetoclax/Acalabrutinib
DrugAll 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.
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.
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