Acalabrutinib study in Indian patients with chronic lymphocytic leukaemia & relapsed and refractory mantle cell lymphoma

Inclusion Criteria

• Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the exclusion criteria apply:
• 1. Men and Women aged 18yrs or more.
• 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2
• 3. Able to receive all outpatient treatments, all laboratory monitoring, and all radiologic evaluations.
• 4. The following laboratory parameters:
• a. Absolute neutrophil count (ANC) ≥750 cells/μL or ≥500 cells/μL in patients with documented bone marrow involvement, and independent of growth factor support 07 days before the assessment
• b. Platelet count ≥50,000 cells/μL or ≥30,000 cells/μL in patients with documented bone marrow involvement, and without transfusion support 07 days before the assessment
• c. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.0 x ULN
• d. Total bilirubin ≤1.5 x ULN
• e. Estimated creatinine clearance of ≥30 mL/min
• 5. Refractory disease defined as achieving less than partial response with the most recent treatment within 6 months before study entry
• 6. Provision of signed, written and dated informed consent prior to any study-specific Procedures
• 7. The patients of either CLL or MCL:
• a. CLL patients:
• i. Treatment naïve or ≥1 prior systemic therapy for CLL
• ii. Diagnosis of CD20+ CLL that meets published diagnostic criteria (Hallek et al. 2018)
• iii. An active disease that meets ≥1 of the following iwCLL 2018 criteria for requiring treatment:
• 1) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia. Cut-off levels of Hb <10 g/dL or platelet counts <100 × 109/L are generally regarded as an indication for treatment. However, in some patients, platelet counts <100 × 109/L may remain stable over a long period; this situation does not automatically require therapeutic intervention.
• 2) Massive (i.e., ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
• 3) Massive nodes (i.e., ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
• 4) Progressive lymphocytosis with an increase of ≥50% over a 2-month period or Lymphocyte Doubling Time (LDT) in <6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; patients with initial blood lymphocyte counts <30 × 109/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (e.g., infections, steroid administration) should be excluded.
• 5) Autoimmune complications, including anaemia or thrombocytopenia poorly responsive to corticosteroids.
• 6) Symptomatic or functional extra-nodal involvement (e.g., skin, kidney, lung, spine).
• 7) Disease-related symptoms as defined by any of the following:
• a) Unintentional weight loss of ≥10% within the previous 06 months.
• b) Significant fatigue (i.e., ECOG performance scale 02 or worse; cannot work or unable to perform usual activities).
• c) Fever ≥100.5°F or 38.0°C for 02 or more weeks without evidence of infection.
• d) Night sweats for ≥1 month without evidence of infection.
• b. MCL Patients:
• i. Confirmed MCL with translocation t(11;14) (q13;q32) and/or overexpressed cyclin D1
• ii. Measurable nodal disease (one or more lesions measuring ≥2 cm in the longest diameter)
• iii. Relapsed after, or were refractory to, 1-5 previous treatments