Leukemia D8220C00008 (Heme)

This is a global, Phase 3b, multicenter, open-label, single-arm study to evaluate the safety and efficacy of acalabrutinib 100 mg bid in approximately 600 participants with chronic lymphocytic leukemia (CLL). Participants will be enrolled into 3 cohorts: treatment-naive (TN), relapsed/refractory (R/R), and prior Bruton tyrosine kinase inhibitor (BTKi) therapy. Participants will remain on study treatment until completion of 48 cycles (28 days per cycle), disease progression, toxicity requiring discontinuation, withdrawal of consent, lost to follow-up, death, or study termination by the sponsor whichever occurs first. The duration of the study will be approximately 72 months from the first participant enrolled. This duration includes an estimated 24-month recruitment time and an assumed 48 cycles of study treatment (28 days per cycle); additional study time will be accrued during the follow-up period for those participants remaining on study treatment after completion of 48 cycles (the amount of time will vary by participant).

Eligibility Criteria:

  1. Men and women ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place)
  2. Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018):
    1. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥1 B-cell marker (CD19, CD20, and CD23) and CD5
    2. Prolymphocytes may comprise <55% of blood lymphocytes
    3. Presence of ≥5 × 109 B lymphocytes/L (5000/μL) in the peripheral blood (at any point since the initial diagnosis)
  3. Active disease as per at least 1 of the following IWCLL 2018 criteria
    1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin <10 g/dL) and/or thrombocytopenia (platelets <100,000/μL).
    2. Massive (i.e., ≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
    3. Massive nodes (i.e., ≥10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy
    4. Progressive lymphocytosis with an increase of >50% over a 2-month period or a lymphocyte doubling time (LDT) of <6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte count obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of <30x109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
    5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
    6. B-symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥1 of the following disease-related symptoms or signs: o- Unintentional weight loss ≥10% within the previous 6 months before screening o- Significant fatigue (Eastern Cooperative Oncology Group [ECOG] performance status ≥2; inability to work or perform usual activities) o- Fevers higher than 100.5°F or 38.0°C for ≥2 weeks before screening without evidence of infection o- Night sweats for ≥1 month before screening without evidence of infection

Available at: Hartford Hospital, Hospital of Central Connecticut

Cancer Clinical Research Office