CLL08 – A study to evaluate the efficacy of venetoclax/rituximab (VenR) re-treatment in relapsed/refractory Chronic Lymphocytic Leukaemia (CLL) patients with disease progression following VenR as their last line of therapy.

ACTRN 12623000640606

Brief Summary

The purpose of this study is to evaluate the efficacy of retreatment with Venetoclax and Rituximab in relapsethe return of disease and refractory CLL patients.

Intervention/Treatment

• Drug: Ventoclax.
• Drug: Rituximab.

Inclusion Criteria

1. Signed informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
2. Age 18 years or above.
3. Diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of CLL that meets published diagnostic criteria:
   • Patients must have peripheral bloodthe red bodily fluid that transports oxygen and other nutrients around the body B-lymphocyte counts which clonally express CD5, CD19, CD20, and CD23 and are either kappa or lambda light-chain-restricted.
   • Prolymphocytes may comprise no more than 55per cent of total circulating lymphocytes. At initial diagnosis of CLL (i.e. prior to front-line treatment), the peripheral lymphocyte count must have been > 5000 per mm3.
   • Patients must meet the following criteria for relapsed or refractory CLL (per the iwCLL guidelines:
     1. Relapsed disease: a patient who previously achieved a CR or PR, but after a period of 6 months or more demonstrates evidence of progression.
     2. Refractory disease: treatment failure or disease progression within 6 months of the last anti-leukaemia therapy.
4. Completed a full, 24-month course of VenR for relapsed/refractory CLL with a clinical response, defined as partial response or complete response with or without incomplete count recovery.
5. Subsequent disease progression meeting iwCLL criteria for treatment, at least 12 months after completion of VenR therapy:
   • Cohort 1: disease progression between 12-24 months after completion of VenR.
   • Cohort 2: disease progression greater than 24 months after completion of VenR.
6. ECOG performance score of less than or equal to 1.
7. Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells function without growth factor or transfusion support, defined as:
   • Haemoglobin greater than 8 g per dL without transfusion support within 2 weeks of screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening.
   • Absolute neutrophil count (ANC) greater than 500/mm3 – the use of G-CSF to achieve this is permitted.
   • Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding greater than 50,000/mm3.
   • If any of the above cytopenias are present, there should be no evidence of myelodysplastic syndrome (MDS) or hypoplastic bone marrow.
8. Adequate renal and hepatic function defined as:
   • CrCl greater than 30mL per minute using 24-hour creatinine clearance or modified Cockcroft-Gault equation using ideal body massa growth of cells that come together to make a lump, may or may not be cancer (IBM) instead of mass.
   • AST and ALT less than 5 x upper limit of normal (ULN) of institution’s normal range.
   • Bilirubin less than 1.5 x ULN (except patients with Gilbert’s syndrome).
   • PT/INR and APTT less than 1.2 x ULN of institution’s normal range. Patients with an elevated prothrombin time and known lupus anticoagulantmedication used to prevent or reduce blood clots; also known as blood thinners may be eligible for participation after consulting the Medical Monitorto check on, keep track of.
9. Female patients must be surgically sterile, postmenopausal (for at least 1 year) or have negative results for a pregnancy test:
   • At screening, on a serum sample obtained within 14 days prior to initiation of study treatment, and
   • Prior to dosing, on a urine sample obtained on Week 1, Day 1 if it has been more than 7 days since obtaining the serum pregnancy test result.
10. Females of childbearing potential must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 12 months after completing therapy with rituximab:
    • Total abstinence from sexual intercourse.
    • A vasectomised partner.
    • Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) that started at least 3 months prior to study drug administration.
    • Double-barrier method (condom + diaphragm or cervical cup with spermicidal contraceptive sponge, jellies or cream).
11. Non-vasectomised must practice at least one of the following methods of birth control throughout the duration of study participation and for at least 12 months after completing therapy with rituximab:
    • Total abstinence from sexual intercourse.
    • A partner who is surgically sterile or postmenopausal (for least 1 year) or who is taking hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to study drug administration.
    • Double-barrier method (condom + diaphragm or cervical cup with spermicidal contraceptive sponge, jellies or cream).
12. Patients must agree not to donate blood, semen or sperm while on study treatment and for at least 12 months after treatment discontinuation.
13. Patients may be eligible if they are able to be taken off warfarin and started on an alternative anticoagulant.
14. Prior BTKi therapy is permitted.
15. Those with history of the below prior other malignancy may be eligible:
    • Curatively treated basal cell carcinomacancer arising from tissues that line organs or squamous cell carcinoma of the skin or carcinoma in situpre-cancerous condition where abnormal cells haven't spread beyond the place they developed of the cervix at any time prior to study.
    • Other cancers not specified above which have been curatively treated by surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence and/or radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, from which patient is disease-free for greater than or equal to 5 years without further treatment.