Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies

A Phase 1/2 Open Label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies

This is an open-label, two-part study to assess the safety, tolerability, pharmacokinetics and clinical efficacy of acalabrutinib in Chinese adult subjects with R/R MCL, CLL and other B-cell malignancies. The study is divided into 2 parts: Phase 1 portion and Phase 2 portion.

Inclusion Criteria

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Chinese subjects at least 18 years of age at the time of study entry.
3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
4. Adequate hematological and organ function.
5. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
6. Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14) (q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5). Disease had relapsed after or been refractory to previous treatment.
7. Diagnosis of CLL that meets published diagnostic criteria. Must have received ≥ 1 prior systemic therapies for CLL.
8. Active disease per iwCLL 2018 criteria that requires treatment. (CLL only)
9. Other relapsed/refractory B-cell malignancies without stand of care (phase 1 only).

Exclusion criteria

1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to <2 years.
2. Significant cardiovascular disease.
3. Known central nervous system involvement of lymphoma/leukemia or leptomeningeal disease.
4. Known history of HIV, serologic status reflecting active hepatitis B or C infection.
5. Major surgery within 4 weeks before first dose of study drugs.
6. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
7. Required or received anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon).
8. Prior exposure to a BCR or BCL-2 inhibitor.
9. Use of a strong inhibitor or inducer of CYP3A.
10. Breastfeeding or pregnant.