A Phase 3 Study of DZD8586 versus Investigator’s Choice in r/r CLL/SLL

You may be able to join if

• Patients must provide a voluntarily signed and dated written informed consent prior to any study-specific procedures, sampling and analyses.
• Female patient should use adequate contraception such as sexual abstinence, tubal ligation, use of hormonal contraception with known low risk of drug interactions (Levonorgestrel intra uterine system [Mirena], medroxyprogesterone injection [Depo Provera]), copperbanded intra-uterine devices, and partner vasectomy during the study and until 3 months after the last dose of DZD8586/idelalisib, 6 months after the last dose of bendamustine, and 12 months after the last dose of rituximab, whichever is longer. All hormonal contraception methods (except abstinence) should be used in combination with the use of condoms by their male sexual partners. Female patient should not breastfeed. Female patient of potential conception should have a negative pregnancy test prior to initiation of study treatment. Female patient may be enrolled if they meet one of the following criteria: • Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatment. Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels falling within the post-menopausal range. • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (excluding tubal ligation).
• Male and female patients must be ≥ 18 years of age when signing the informed consent form.
• Patients must exhibit Eastern Cooperative Oncology Group (ECOG) performance status 0- 2 with no disease deterioration over the previous 2 weeks.
• 4a. Patients diagnosed with CLL/SLL per iwCLL 2018 criteria and meet the following conditions: • Relapsed, refractory or intolerable during or after any previous BTK inhibitor treatment. o The definitions of refractory and relapsed are defined according to the following criteria: a. Refractory: disease progression during treatment or within 6 months after achieving response. b. Relapse: disease progression after achieving partial response (PR) or greater response with prior therapy for at least 6 months. BTK inhibitor therapy is refractory if stable disease (SD) is the best response after treatment with standard dose for 6 months; participants who have disease progression during treatment should be treated with BTK inhibitor for no less than 8 weeks; participants who achieve response after treatment should continue treatment until disease progression or for no less than 6 months after achieving response. o BTK inhibitor intolerant events are defined as the cessation of treatment due to one of the following reasons (drug-related rather than disease-related), despite the best medical treatment, determined by the investigator to be drug-related or potentially drug-related toxicities: a. The same ≥ Grade 2 non-hematological toxicity lasted for ≥ 7 days and recurred twice or more. b. The same ≥ Grade 3 non-hematological toxicity lasted for ≥ 7 days or recurred twice or more (regardless of duration). c. Grade 4 non-hematological toxicity (regardless of duration). d. The same ≥ Grade 3 hematological toxicity lasted for ≥ 7 days and recurred twice or more. e. Grade 3/4 neutropenia with infection or fever (regardless of duration). f. Grade 3 thrombocytopenia with significant clinical bleeding. g. Grade 4 hematological toxicity lasted for ≥ 7 days, or the same Grade 4 hematological toxicity recurred twice or more (regardless of duration). h. Grade 2 or higher, and the risk of adverse events judged by the investigator was high (including but not limited to cardiac and cerebrovascular events, severe bleeding, severe allergy, etc.).
• 4b. • Per the status of the approved drugs in the European countries and clinical practice, patients should have been previously treated with BCL-2 inhibitor according to local clinical practice. • Life expectancy ≥ 3 months. • The patient must meet the criteria for clinical treatment for r/r CLL/SLL based on the iwCLL 2018 guideline, and the investigator judges there’s a need for clinical treatment: o Criteria for initiation of subsequent therapy are met, including persistence of disease burden after front-line therapy and unresolved indications of front-line therapy. o Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. o Massive (i.e., ≥ 6 cm below the left costal margin) or progressive or symptomatic splenomegaly. o Massive nodes (i.e., ≥ 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. o Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period, or lymphocyte doubling time (LDT) < 6 months. Factors contributing to lymphocytosis other than CLL (e.g., infections, steroid administration) should be excluded. o Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine). o Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids. o Disease-related symptoms as defined by any of the following: unintentional weight loss ≥ 10% within the previous 6 months; significant fatigue (e.g., ECOG performance scale 2 or worse; unable to perform usual activities); fevers ≥ 100.5°F or 38.0°C for 2 or more weeks without evidence of infection; night sweats for ≥ 1 month without evidence of infection.