CTRI/2026/01/101003 [Registered on: 13/01/2026] Trial Registered Prospectively
Last Modified On:
10/02/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A clinical trial to study the efficacy and safety of a drug in treated patients having chronic lymphocytic leukemia or small lymphocytic lymphoma
Scientific Title of Study
A Global Multicenter, Open Label, Randomized Phase 3 Registrational Study of Lisaftoclax (APG-2575) in Previously Treated Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Trial Acronym
GLORA Study
Secondary IDs if Any
Secondary ID
Identifier
137639
Other
2023-508005-24
Other
APG2575CG301 Version 2.1 GL dated 29 Mar 2025
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Australia Belgium Bulgaria Canada China Czech Republic France Germany Hungary India Israel Italy Poland Romania Russian Federation Slovakia Spain Turkey United Kingdom United States of America
40, Sassoon Road, Pune- 411001, Maharashtra, India Pune MAHARASHTRA
020-66455495 020-66455628 bmtpune@gmail.com
Dr Nataraj K S
Healthcare Global Enterprise Limited
#8, HCG Towers, P. Kalinga Rao Road, Sampangi Rama Nagar, Bengaluru, Karnataka- 560027, India Bangalore KARNATAKA
9482141773 9482141773 drnataraj.ks@hcge1.com
Dr Ajay Gupta
Indraprastha Apollo Hospitals
Sarita Vihar, Delhi-Mathura Road,
New Delhi - 110076 New Delhi DELHI
91 7838013018
oncol@rediffmail.com
Dr Ranjit Kumar Sahoo
Institute of Rotary Cancer Hospital All India Institute of Medical Sciences
Room No. 218, 2nd Floor, Department of Medical Oncology, IRCH Building, Ansari Nagar, New Delhi 110029
New Delhi DELHI
91-9013956187
drranjitmd@gmail.com
Dr Prasanth Ganesan
Jawaharlal Institute of Postgraduate Medical Education and Research, JIPMER
SSB, 3rd Floor, Department of Medical Oncology, JIPMER campus road, Gorimedu, Dhanvantari Nagar, Puducherry – 605006
Pondicherry PONDICHERRY
91-9444216310
pg1980@gmail.com
Dr Atul Sharma
Max Super Speciality Hospital
Saket (East Block) – A unit of Devki Devi Foundation, Department of Oncology, Service Floor, 2, Press Enclave Road, Saket, New Delhi – 110017
New Delhi DELHI
Institutional Ethics Committee- Clinical Studies, Apollo Hospitals, Bannerghatta Road
Approved
Institutional Ethics Committee- Clinical Studies, Apollo Speciality Hospital, Madurai
Approved
Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Centre
Approved
Medanta Institutional Ethics Committee (MIEC)
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C911||Chronic lymphocytic leukemia of B-cell type,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
BTKi
A. Acalabrutinib (CALQUENCE®) capsule is given orally at 100 mg twice daily as per Package Insert
B. Ibrutinib (IMBRUVICA) capsules is given orally at 420 mg once daily as per Package Insert
C. Zanubrutinib (BRUKINSA) is given orally at 160 mg twice daily or 320 mg once daily as per Package Insert/Product Information – NOTE – this treatment is not available for enrolment in India.
Intervention
Lisaftoclax (APG-2575) Plus BTKi
Route of Administration - Oral
Lisaftoclax (APG-2575) is administered orally once daily at escalating doses ranging from 20 mg to 400 mg during daily ramp-up, and at 400 mg QD on a continuous basis
Study Duration – 4-7 years
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1 Age 18 years or above
2 Patients that have documented CLL or SLL who meet iwCLL 2018 criteria for CLL treatment guidelines are eligible.
A Received a BTKi (acalabrutinib, ibrutinib, or zanubrutinib) monotherapy as 1st, 2nd, or 3rd line therapy for 12 months and have best response as either a or b
a Stable disease
b PR with any of the following baseline risk factors:
Lymph node(s) diameter greater or equal to 2.5 CM
ALC greater or equal to 25 into 109 per L
Have greater or equal to 1 high risk factor(s) (del17p or p53mut, unmutated IGHV, complex karyotype greater or equal to 5 factors (greater or equal to 3 chromosomal abnormalities and greater or equal to 1 biological or structural aberrations)
3 ECOG Performance Status grade 0 to 2
4 Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of randomization as follows:
a Absolute neutrophil count greater or equal to 1.0 into 109 per L
b Platelet counts greater or equal to 75 into 109 per L, in cases of thrombocytopenia
c Total hemoglobin greater or equal to 9 g per dL
5 Adequate renal function
Creatinine clearance must be greater than 50 ml per min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men- GFR approx ((140 - age) multiply actual body weight)slash(72 into creatinine), for women into 0.85) or an equally accurate method.
ExclusionCriteria
Details
Patients who meet any of the following exclusion criteria are not to be enrolled in this study.
1 Achieved complete response (CR) or CRi status or disease progression while on BTKi (acalabrutinib, ibrutinib, zanubrutinib) monotherapy prior to study entry.
2 Transformation of CLL to Richter’s condition.
3 Prior treatment with venetoclax or other Bcl-2 inhibitors.
4 An individual organ or system impairment score of 4 as assessed by the cumulative illness rating scale (CIRS) definition limiting the ability to receive the study treatment, or any other life threatening illness, medical condition, or organ system dysfunction that, in the investigator´s opinion, could compromise the patients’ safety or interfere with the absorption or metabolism of the study drugs (e.g. inability to swallow tablets or impaired resorption in the gastrointestinal tract).
5 Patients receiving acalabrutinib capsule-based therapy (and not acalabrutinib tablet) who require treatment with proton pump inhibitors (e.g, omeprazole esomeprazole, lansoprazole etc,) at study entry. (Patients receiving proton pump inhibitors who switch to H2 receptors antagonists or antacids are eligible for enrollment).
6 Patients who require or are receiving anticoagulation therapy with warfarin or equivalent vitamin K antagonists within 7 days of first dose of the study drug(s).
7 Patients who are pregnant or breastfeeding.
8 Has received the following within 7 days prior to the first dose of study drug:
a Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for antineoplastic intent.
b CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin or potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John’s wort.
9 Radiation within 14 days of study entry
10 Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to less than or equal to grade 1 or baseline, except alopecia or neuropathy.
11 Failure to recover, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days and minor surgery such as a biopsy within 14 days from first dose of study drug.
12 QTcF interval 480ms or other remarkable abnormality of ECG, including second-degree type II atrioventricular block, third-degree atrioventricular block, or bradycardia (ventricular rate consistently less than 50 beats per minute).
13 Underlying clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening or any
14 Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
15 Uncontrolled medical condition (e.g., diabetes).
16 Known to have central nervous system (CNS) involvement.
17 Prior malignancy within 2 years of treatment that required radiotherapy, or systemic therapy.
18 Patients treated with strong CYP3A4 inhibitors or inducers (patients can be washed out allowing 5 half-lives prior to study treatment and or switched to non-prohibited drug).
19 History of stroke or intracranial hemorrhage within 3 months prior to registration for study screening or known bleeding disorders
20 Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
21 Vaccination with live vaccines within 14 days prior to screening.
22 Active infection requiring systemic antibiotic or antifungal medication, known clinically active hepatitis B or C, or HIV, HCV infection or active COVID-19. (Patients who have received COVID-19 vaccination will be considered as eligible for the study.)
23 Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of study treatment, further pregnancy testing will be performed monthly).
24 Fertile men or women of child bearing potential unless, surgically sterile or greater than or equal to 2 years after the onset of menopause or willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index less than 1) and one additional effective (barrier) method during study treatment and for 3 months after the end of study treatment
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To evaluate the progression-free survival (PFS) of lisaftoclax in combination with a BTKi compared with BTKi monotherapy in CLL or SLL patients previously treated with a BTKi, as determined by independent radiological review committee (IRC) using the iwCLL guidelines
12 months
Secondary Outcome
Outcome
TimePoints
To evaluate overall survival (OS) of lisaftoclax in combination with a BTKi versus BTKi monotherapy.
12 months
Other Secondary Objectives
1 To determine efficacy of lisaftoclax plus a BTKi, compared with BTKi monotherapy by additional outcome measures including PFS by investigators, ORR rate, CR/CRi rate, DoR, uMRD rate.
2 To evaluate safety of lisaftoclax plus a BTKi, versus BTKi monotherapy
3 To characterize the population pharmacokinetics of lisaftoclax
4 To evaluate Patient-Reported Outcome (PRO) measures of lisaftoclax plus a BTKi versus BTKi monotherapy based on EORTC QLQ-C30
5 To evaluate Health Economics Outcomes Research (HEOR) measures of lisaftoclax plus BTKi versus BTKi monoherapy based on Europol 5 Dimension (EQ-5D-5L)
12 months
Target Sample Size
Total Sample Size="440" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
30/01/2026
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
23/01/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="4" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a global multicenter, open label, randomized pivotal phase 3 study to evaluate efficacy and safety of lisaftoclax in combination with a BTKi in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL or SLL) who were previously treated with a BTKi.
Number of Subjects
Approximately 440 eligible patients with CLL or SLL who have been on a BTKi for at least 12 months as first line, second line or third line of therapy will be randomized in a 1:1 ratio to either the Investigational Arm (lisaftoclax in combination with a BTKi used prior to study entry) or Control Arm (continue on the same BTKi), BTKi includes acalabrutinib, ibrutinib or zanubrutinib.
Lisaftoclax (APG-2575) is administered orally once daily at escalating doses ranging from 20 mg to 400 mg during daily ramp-up, and at 400 mg QD on a continuous basis.
Duration of treatment:
Patients in both the investigational and control arms will be treated until progression, unacceptable toxicity, withdrawal of consent, start of alternate therapy or for administrative reasons deemed necessary by the Sponsor, whichever occurs first.