Acalabrutinib Study in Indian Patients With Chronic Lymphocytic Leukaemia & Relapsed and Refractory Mantle Cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
This study is plan to assess the safety and efficacy of Acalabrutinib in Indian patients with chronic lymphocytic leukaemia (CLL) and relapsed and refractory mantle cell lymphoma (MCL)

Detailed Description
-----------------
A prospective, multi-centre, phase IV clinical trial of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia (CLL) and relapsed and refractory mantle cell lymphoma (MCL). As per recommendation from Indian health authority, the current phase-IV study is planned with the aim to assess the safety and efficacy profile of Acalabrutinib in Indian patients with CLL/SLL, and patients with MCL who have received at least one prior therapy. The data obtained from the study will help to understand the safety and efficacy profile of Acalabrutinib in Indian patients. Patients will be monitored throughout the study period for Adverse Events of Acalabrutinib

Official Title
-----------------
A Prospective, Multi-centre, Phase IV Clinical Trial to Assess the Safety and Efficacy of Acalabrutinib Capsules in Indian Adult Patients With Chronic Lymphocytic Leukaemia and Relapsed and Refractory Mantle Cell Lymphoma.

Conditions
-----------------
Chronic Lymphocytic Leukemia and Relapsed and Refractory Mantle Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: Acalabrutinib capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
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: 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 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 Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.0 x ULN Total bilirubin ≤1.5 x ULN 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: 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. Massive (i.e., ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly. Massive nodes (i.e., ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. 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. Autoimmune complications, including anaemia or thrombocytopenia poorly responsive to corticosteroids. Symptomatic or functional extra-nodal involvement (e.g., skin, kidney, lung, spine). Disease-related symptoms as defined by any of the following: Unintentional weight loss of ≥10% within the previous 06 months. Significant fatigue (i.e., ECOG performance scale 02 or worse; cannot work or unable to perform usual activities). Fever ≥100.5°F or 38.0°C for 02 or more weeks without evidence of infection. 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 Exclusion Criteria: Known prolymphocytic leukaemia, Central Nervous System (CNS) lymphoma or leukaemia; or known history of (or currently suspected) Richter's syndrome Treatment with chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days of the first dose of study drug Prior radio-conjugated or toxin-conjugated antibody therapy Anticoagulation therapy (e.g., warfarin or equivalent vitamin K antagonists) within 07 days of the first dose of study drug. Major surgery ≤30 days before the first dose of study drug History of stroke or intracranial haemorrhage ≤6 months before the first dose of study drug History of bleeding diathesis Prior exposure to a B-cell lymphoma-2 (Bcl-2) inhibitor or B-cell receptor inhibitor like BTKs Active Cytomegalovirus (CMV) infection or serologic status reflecting active Hepatitis B or C infection or known history of infection with Human Immunodeficiency Virus (HIV), or any uncontrolled active systemic infection. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Congestive Heart Failure, or Myocardial Infarction within 06 months of screening, or any Class 3 or 4 cardiac diseases as defined by the New York Heart Association Functional Classification, or QTcB >480 msec at screening. Requiring treatment with proton-pump inhibitors (e.g., Omeprazole, Esomeprazole, Lansoprazole, Dexlansoprazole, Rabeprazole, or Pantoprazole). Breastfeeding or pregnant. Current life-threatening illness, medical condition, or organ/system dysfunction which, in the Investigator's opinion, could have compromised the subject's safety or put the study at risk. Concurrent participation in another therapeutic clinical trial. -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A Prospective, Multicentre, Phase-IV study and Clinical trials with a single arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acalabrutinib Capsule<br>Single-arm study | Drug: Acalabrutinib capsule<br>* The recommended dose of Acalabrutinib is 100 mg given per oral (PO) twice daily<br>* Other names: Calquence®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia and relapsed and refractory mantle cell lymphoma | Number, frequency and percentages of subjects with adverse events (AEs) and serious adverse events (SAEs). | 6 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia and relapsed and refractory mantle cell lymphoma | Objective response rate | 3 Month and 6 Month | 
| Patient reported outcome | Health related quality of life Questionnaire evaluation for patient reported outcome. | 3 Month and 6 Month |