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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04930536
• Collaborator: (none)
• Enrollment: 100
• Locations: 15
• Arm: 1
• Anticipated Duration (Months): 14.7
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia and Relapsed and Refractory Mantle Cell Lymphoma	Drug: Acalabrutinib capsule	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A Prospective, Multicentre, Phase-IV study and Clinical trials with a single arm.A Prospective, Multicentre, Phase-IV study and Clinical trials with a single arm.
• Masking: None (Open Label)
• Masking Description: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jul 14, 2021
• Anticipated Primary Completion Date: Oct 3, 2022
• Anticipated Study Completion Date: Oct 3, 2022

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

1. To assess the safety of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia and relapsed and refractory mantle cell lymphoma [6 Month]

   Number, frequency and percentages of subjects with adverse events (AEs) and serious adverse events (SAEs).

Secondary Outcome Measures

1. To assess the efficacy of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia and relapsed and refractory mantle cell lymphoma [3 Month and 6 Month]

   Objective response rate

2. Patient reported outcome [3 Month and 6 Month]

   Health related quality of life Questionnaire evaluation for patient reported outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

2. The following laboratory parameters:

3. 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

4. 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

5. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.0 x ULN

6. Total bilirubin ≤1.5 x ULN

7. 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:

1. 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:

8. Unintentional weight loss of ≥10% within the previous 06 months.

9. Significant fatigue (i.e., ECOG performance scale 02 or worse; cannot work or unable to perform usual activities).

10. Fever ≥100.5°F or 38.0°C for 02 or more weeks without evidence of infection.

11. Night sweats for ≥1 month without evidence of infection.

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Ahmedabad		India	380009
2	Research Site	Bangalore		India	560017
3	Research Site	Bangalore		India	560064
4	Research Site	Bengaluru		India	560099
5	Research Site	Chandigarh		India	160012
6	Research Site	Gurugram		India	122001
7	Research Site	Guwahati		India	781032
8	Research Site	Hyderabad		India	500019
9	Research Site	Hyderabad		India	500033
10	Research Site	Kochi		India	682041
11	Research Site	Kolkata		India	700160
12	Research Site	Ludhiana		India	141 008
13	Research Site	Mumbai		India	400012
14	Research Site	Mumbai		India
15	Research Site	New Delhi		India	110 085

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04930536
• Other Study ID Numbers: D8220C00022
• First Posted: Jun 18, 2021
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Acalabrutinib

Study Results

No Results Posted as of Aug 5, 2022