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

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.

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)

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia and Relapsed and Refractory Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Acalabrutinib capsule

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

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Ahmedabad, India, 380009
    • Research Site
  • Bangalore, India, 560017
    • Research Site
  • Bangalore, India, 560064
    • Research Site
  • Bengaluru, India, 560099
    • Research Site
  • Chandigarh, India, 160012
    • Research Site
  • Gurugram, India, 122001
    • Research Site
  • Guwahati, India, 781032
    • Research Site
  • Hyderabad, India, 500019
    • Research Site
  • Hyderabad, India, 500033
    • Research Site
  • Kochi, India, 682041
    • Research Site
  • Kolkata, India, 700160
    • Research Site
  • Ludhiana, India, 141 008
    • Research Site
  • Mumbai, India, 400012
    • Research Site
  • Mumbai, India, 400010
    • Research Site
  • New Delhi, India, 110 085
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. 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
2. 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
3. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.0 x ULN
4. Total bilirubin ≤1.5 x ULN
5. 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:

   1. Unintentional weight loss of ≥10% within the previous 06 months.
   2. Significant fatigue (i.e., ECOG performance scale 02 or worse; cannot work or unable to perform usual activities).
   3. Fever ≥100.5°F or 38.0°C for 02 or more weeks without evidence of infection.
   4. 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:

1. Known prolymphocytic leukaemia, Central Nervous System (CNS) lymphoma or leukaemia; or known history of (or currently suspected) Richter's syndrome
2. Treatment with chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days of the first dose of study drug
3. Prior radio-conjugated or toxin-conjugated antibody therapy
4. Anticoagulation therapy (e.g., warfarin or equivalent vitamin K antagonists) within 07 days of the first dose of study drug.
5. Major surgery ≤30 days before the first dose of study drug
6. History of stroke or intracranial haemorrhage ≤6 months before the first dose of study drug
7. History of bleeding diathesis
8. Prior exposure to a B-cell lymphoma-2 (Bcl-2) inhibitor or B-cell receptor inhibitor like BTKs
9. 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.
10. 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.
11. Requiring treatment with proton-pump inhibitors (e.g., Omeprazole, Esomeprazole, Lansoprazole, Dexlansoprazole, Rabeprazole, or Pantoprazole).
12. Breastfeeding or pregnant.
13. 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.

14. Concurrent participation in another therapeutic clinical trial.

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events of Special Interest (AESI) Including Arrhythmias (Atrial Fibrillation), Anaemia, Hypertension, Bleeding, Infections	The AESIs for acalabrutinib, including arrhythmias (atrial fibrillation), anaemia, hypertension, bleeding, and infections, are presented.	Throughout study completion, approximately 198 days (from the Screening Phase [Day 0], Treatment Phase [Days 1-170], and until the Follow-up Phase [28 days after Day 170])
Second Primary Malignancies	The safety of acalabrutinib was investigated by determining the number of second primary malignancies.	Throughout study completion, approximately 198 days (from the Screening Phase [Day 0], Treatment Phase [Days 1-170], and until the Follow-up Phase [28 days after Day 170])

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response to Treatment	The efficacy of acalabrutinib was assessed by measuring the participants' objective response to treatment. Objective response = Complete Response (CR) + Partial Response (PR) + Partial Response with lymphocytosis (PRL).	Visit 5 (Day 85) and Visit 8 (Day 170)
Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire)	The EORTC QLQ-C30 is a 30-item questionnaire that measures quality of life in cancer patients. It is divided into several scales: Functioning Scales (Physical, Role, Cognitive, Emotional, and Social), Symptom Scales (Fatigue, Pain, Nausea/Vomiting), Dyspnoea, Sleep Disturbances, Appetite Loss, Diarrhoea, Constipation, Financial Difficulties, and Global Health Status/Quality of Life Scale. Scores range from 0 to 100. A higher score indicates better health related quality of life. The total scores were calculated from the mean of the 13 QLQ-C30 scales (Global Quality of Life Scale and Financial Impact Scale were excluded). Prior to calculating the mean, Symptom Scales were reversed to obtain a uniform direction of all scales. The total score was only calculated if all of the required 13 scale scores were available using scale scores based on the completed items, provided that at least 50% of the items in that scale were completed.	From Visit 1 (Day 0), during Visit 5 (Day 85), and at Visit 8 (Day 170)

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CSP_redacted
• SAP_redacted
• CSR_synopsis-redacted

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): May 2, 2023

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Leukemia; Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Acalabrutinib
• Other Study ID Numbers: D8220C00022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No