Acalabrutinib and Venetoclax for relapsed CLL/SLL after initial BTKi+BCL2i response

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 2 study investigates whether a fixed-duration treatment with acalabrutinib plus venetoclax can provide an effective second-line option for relapsed CLL/SLL patients who previously responded to first-line BTKi+BCL2i therapy. Eligible participants are adults with relapsed disease who achieved PR or better for at least 2 years after 1L therapy and have specified IGHV/TP53 risk profiles. The study will assess overall response rate and safety over up to 5 years per participant, with groups defined by disease risk. Treatment consists of acalabrutinib and venetoclax, followed by post-treatment follow-up after the intervention.

Why it matters

Who can join: the full rules

Main Inclusion Criteria:

1. Participant must be ≥ 18 years at the time of signing informed consent.
2. Diagnosis of relapsed CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018) in need of treatment.
3. Participants must have received only one prior first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) for a minimum of 2 years since the end of the prior 1L treatment.
4. The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:

   1. IGHV (mutated vs. unmutated)
   2. del(17p) (present or absent)
   3. TP53 mutation (present or absent)
5. ECOG performance status 0, 1 or 2
6. Adequate organ and bone marrow (BM) function.

Main Exclusion Criteria:

1. Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
2. Significant cardiovascular or cerebrovascular disease.
3. Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
4. Child-Pugh B/C liver cirrhosis.
5. History of prior or current malignancy.
6. HIV positive
7. History of progressive multifocal leukoencephalopathy (PML).
8. Active hepatitis B or C infection:
9. Corticosteroid use \> 20 mg within 1 week before the first dose of study intervention.
10. History of hypersensitivity or anaphylaxis to study intervention(s).
11. Requires treatment with a strong CYP3A4 inhibitor/inducer.
12. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
13. Major surgical procedure within 30 days of the first dose of study intervention.

Where it's running

• Research Site
  Boston, Massachusetts, United States Recruiting
• Research Site
  Charlotte, North Carolina, United States Recruiting
• Research Site
  Durham, North Carolina, United States Recruiting
• Research Site
  Winston-Salem, North Carolina, United States Recruiting
• Research Site
  Horn, Austria Recruiting
• Research Site
  Dublin, Ireland Recruiting

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center
• Email: information.center@astrazeneca.com
• Phone: 1-877-240-9479

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Ibrutinib and Venetoclax in CLL/SLL: Long-Term Outcomes After Frontline CAPTIVATE

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• Immune profiling during first-line pirtobrutinib treatment for CLL/SLL

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• NX-5948 treatment for adults with CLL or SLL after prior BTK and BCL-2 inhibitor therapy

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• Quality of life and symptom changes over two years in adults with CLL or SLL starting targeted therapy

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• Zanubrutinib, obinutuzumab, and sonrotoclax for newly diagnosed CLL or SLL

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• Long-term safety of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.