BridgeMD
A Global Multicenter, Open Label, Randomized Phase 3 Registrational Study of Lisaftoclax (APG-2575) in Previously Treated Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (GLORA Study)
EU CTIS ID: 2023-508005-24-00
What this study is testing
To evaluate the progression-free survival (PFS) of lisaftoclax in combination with a BTKi compared with BTKi monotherapy in CLL/SLL patients previously treated with a BTKi, as determined by independent radiological review committee (IRC) using the iwCLL guidelines (Hallek M et al 2018).
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Aged ≥ 18 years.
- Patients that have documented CLL/SLL who meet iwCLL 2018 criteria for CLL treatment guidelines are eligible. • 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 ≥ 2.5 cm, • ALC ≥ 25x 109 /L • Have ≥ 1 high-risk factor(s) (del17p/p53mut, unmutated IGHV, complex karyotype ≥ 5 factors (≥ 3 chromosomal abnormalities and ≥ 1 biological/structural aberrations).
- ECOG performance status 0-2.
- Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of randomization as follows: • Absolute neutrophil count ≥ 1.0 × 109/L • Platelet counts ≥ 75 × 109/L; in cases of thrombocytopenia • Total hemoglobin ≥ 9 g/dL -.
- Adequate renal function • Creatinine clearance must be > 50 ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 – age) x actual bodyweight) / (72 x creatinine), for women x 0. 85) or an equally accurate method.
- Adequate liver function as indicated by: • Total bilirubin ≤ 1.5 x ULN, except patients with known Gilbert’s Syndrome • Aspartate aminotransferase (AST) ≤ 2.5 x the institutional ULN value • Alanine aminotransferase (ALT) ≤ 2.5 x the institutional ULN value, • International Normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT) ≤ 1.5 × ULN.
You likely can't join if
- Achieved complete response (CR) or CRi status or disease progression while on BTKi (acalabrutinib, ibrutinib, zanubrutinib) monotherapy prior to study entry.
- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ grade 1 or baseline, except alopecia or neuropathy.
- 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.
- 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).
- Underlying clinically significant cardiovascular disease such as: symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening or any cardiovascular disability status of New York Heart Association Class ≥ 2.
- Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
See the full eligibility criteria
Who can join
- Aged ≥ 18 years.
- Patients that have documented CLL/SLL who meet iwCLL 2018 criteria for CLL treatment guidelines are eligible. • 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 ≥ 2.5 cm, • ALC ≥ 25x 109 /L • Have ≥ 1 high-risk factor(s) (del17p/p53mut, unmutated IGHV, complex karyotype ≥ 5 factors (≥ 3 chromosomal abnormalities and ≥ 1 biological/structural aberrations).
- ECOG performance status 0-2.
- Adequate bone marrow function independent of growth factor or transfusion support within 2 weeks of randomization as follows: • Absolute neutrophil count ≥ 1.0 × 109/L • Platelet counts ≥ 75 × 109/L; in cases of thrombocytopenia • Total hemoglobin ≥ 9 g/dL -.
- Adequate renal function • Creatinine clearance must be > 50 ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 – age) x actual bodyweight) / (72 x creatinine), for women x 0. 85) or an equally accurate method.
- Adequate liver function as indicated by: • Total bilirubin ≤ 1.5 x ULN, except patients with known Gilbert’s Syndrome • Aspartate aminotransferase (AST) ≤ 2.5 x the institutional ULN value • Alanine aminotransferase (ALT) ≤ 2.5 x the institutional ULN value, • International Normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT) ≤ 1.5 × ULN.
- Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
What rules you out
- Achieved complete response (CR) or CRi status or disease progression while on BTKi (acalabrutinib, ibrutinib, zanubrutinib) monotherapy prior to study entry.
- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to ≤ grade 1 or baseline, except alopecia or neuropathy.
- 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.
- 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).
- Underlying clinically significant cardiovascular disease such as: symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening or any cardiovascular disability status of New York Heart Association Class ≥ 2.
- Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
- Uncontrolled medical condition (e.g., diabetes).
- Known to have central nervous system (CNS) involvement.
- Prior malignancy within 2 years of treatment that required radiotherapy, or systemic therapy.
- Patients treated with strong CYP3A4 inhibitors/inducers (patients can be washed out allowing 5 half-lives prior to study treatment and/or switched to non-prohibited drug.
- History of stroke or intracranial hemorrhage within 3 months prior to registration for study screening or known bleeding disorders.
- Transformation of CLL to Richter’s condition.
- Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
- Vaccination with live vaccines within 14 days prior to screening (30 days for patients in Czech Republic).
- Active infection requiring systemic antibiotic/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.) (For patients from the Czech Republic, HBV, HCV and HIV testing is mandated at screening for these criteria to be met).
- 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).
- Fertile men or women of childbearing potential unless: surgically sterile or ≥ 2 years after the onset of menopause or willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 3 months after the end of study treatment.
- Prior treatment with venetoclax or other Bcl-2 inhibitors.
- An individual organ/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).
- Patients receiving acalabrutinib capsule-based therapy (not 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).
- 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).
- Patients who are pregnant or breastfeeding.
- Has received the following within 7 days prior to the first dose of study drug: • Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for anti-neoplastic intent. • CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin or potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John’s wort.
- Radiation within 14 days of study entry.
The study team makes the final eligibility decision.
Where it's taking place
- China
- Israel
- Canada
- United States
- Turkey
- United Kingdom
- Russian Federation
- Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include China; Israel; Canada; United States; Turkey; United Kingdom and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.