CTRI/2021/04/033224 [Registered on: 29/04/2021] Trial Registered Prospectively
Last Modified On:
15/05/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A study to see the safety and efficacy of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia and relapsed and refractory mantle cell lymphoma
Scientific Title of Study
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
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
D8220C00022 Version 1.0 Dated 01 Sep 2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
1-100/1/CCH, Nallagandla Village, Serilingampally Mandal , Hyderabad 500019, Telangana, India Hyderabad TELANGANA
9908508805
aribandia@hotmail.com
Dr Neeraj Sidharthan
Amrita Institute of Medical sciences
AIMS Ponekkara, P. O, Kochi-682041
Kerala , India
Ernakulam KERALA
9946047464
neerajsidh@gmail.com
Dr Padmaja Lokireddy
Apollo Hospitals
Apollo Research and Innovations (ARI)
Auditorium Building, 1st Floor, Apollo Medical College, Apollo Hospitals, Jubilee Hills, Hyderabad, Telangana, India- 500096. Hyderabad TELANGANA
9553077700
drloki2002@yahoo.com
Dr Biju George
Christian Medical College
Department of Haematology , Room No. 03 , Christian Medical College, Vellore, Tamil Nadu 632004 Vellore TAMIL NADU
8056416705
biju@cmcvellore.ac.in
Dr Harish
Cytecare Cancer Hospital
Room No 19, Department of Medical Oncology, Venkatala, Bagalur Cross, Yelahanka, Bengaluru, Karnataka 560064 Bangalore KARNATAKA
1st floor, Vedanta Institute of medical sciences, Near Samved Hospital, Stadium Commerce College Road, Navrangpura, Ahmedabad-380009, Gujarat, India Ahmadabad GUJARAT
9824041170
sandip60@yahoo.com
Dr Mallikarjun Kalashetty
Manipal Hospital
1st Floor, Department of Medical Oncology, #98, HAL Airport Road, Bengaluru, Karnataka 560017 Bangalore KARNATAKA
9448781560
mkalashetty@manipalhospitals.com
Dr Sharat Damodar
Mazumbar Shaw Medical Centre
7th Floor, Department of Hemato-Oncology, Narayana Hrudayalaya Limited, Bommasandra Industrial Area, Bangalore, Karnataka - 560099 Bangalore KARNATAKA
Study treatment name: Acalabrutinib; Dosage formulation: Capsule; Route of administration: Per Oral(PO); Dosing instructions :The recommended dose is 100 mg (1 capsule) twice daily. Acalabrutinib should be swallowed whole with water at approximately the same time each day. Acalabrutinib can be taken with or without food. The capsule should not be chewed, dissolved or opened.
Comparator Agent
Not Applicable
Not Applicable
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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
ExclusionCriteria
Details
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.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To investigate the safety of Acalabrutinib
among patients with treatment naïve and
R/R CLL/ SLL, and relapsed & refractory
MCL in Indian patients
Screening visit to 28 days after the last Acalabrutinib dose in the treatment phase.
Secondary Outcome
Outcome
TimePoints
To assess the efficacy of Acalabrutinib in
patients of CLL/SLL and relapsed &
refractory MCL in Indian patients. Patient-reported outcome (PRO)
Baseline
Three Month
Visit 8 (Day 170) End of Treatment Visit
Target Sample Size
Total Sample Size="100" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "103" Final Enrollment numbers achieved (India)="103"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a phase IV, open-label, single-arm,
multi-centre, prospective study.
The study is plans to assess the safety and
efficacy of Acalabrutinib 100 mg capsule in Indian patients. The data obtained
from the study will help to understand the safety and efficacy profile of
Acalabrutinib in Indian patients with chronic lymphocytic
leukaemia (CLL) / Small Lymphocytic
Lymphoma (SLL), and patients with Mantle Cell Lymphoma (MCL) who have received
at least one prior therapy.
The Treatment Phase will be from the start of Cycle
1, Day 1 to end of Cycle 6, Day 28, or until study drug discontinuation due to
either disease progression or unacceptable toxicity or other reasons whichever
occurs earlier. Each cycle of treatment is 28 days.
Patients
will be monitored throughout the study period for Adverse
Events (AEs) / Serious Adverse Events (SAEs) of Acalabrutinib. All
patients who receive Acalabrutinib capsule 100 mg BID will be evaluated for
efficacy once every 03 months during the treatment phase. Safety evaluations
will include clinical laboratory parameters (haematology and biochemistry),
physical examinations, vital sign measurements, ECG monitoring, ECOG
performance status and adverse event monitoring.