RITUXIMAB for Chronic lymphocytic leukemia | Small lymphocytic lymphoma

Inclusion criteria

• {"criterion_text":"- Signed Informed Consent Form\n- Ability and willingness to comply with the requirements of the study protocol\n- Patient must have diagnosis of CLL or SLL that meets published 2018 IWCLL NCI-WG criteria\n- No prior treatment for CLL or SLL including chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal antibody therapy\n- Patient must have an indication for treatment according to published 2018 IWCLL NCI-WG criteria\n- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2\n- Adequate hematologic function independent of growth factor or transfusion support, per local laboratory reference range at screening (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator) defined as follows: o Hemoglobin ≥ 9 g/dL; o Absolute neutrophil count ≥ 1.0 × 109/L; o Platelet count ≥ 50 × 109/L\n- Adequate renal function, per local laboratory reference range at screening, as indicated by: o Calculated creatinine clearance ≥ 30 mL/min using 24-hour Creatinine Clearance or modified Cockcroft-Gault equation (eCCR; with the use of ideal body mass [IBM] instead of mass)\n- Adequate liver function, per local laboratory reference range at screening, as indicated by: o AST and ALT ≤ 2.5 × ULN o Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN for patients with documented Gilbert syndrome)\n- No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment. Patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation\n- No current use of corticosteroids. EXCEPTION: Low doses of steroids (< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted\n- No previous autoimmune complications (e.g. autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and have required treatment with high dose corticosteroids (e.g. equivalent of > 20 mg/day of prednisone), monoclonal antibody-based therapy, or chemotherapy. Prior use of corticosteroids for reasons other than treatment of autoimmune complications of CLL is allowed\n- No major surgery within 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug\n- No radiation therapy ≤ 4 weeks prior to study treatment initiation\n- Patient must be able to receive xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis\n- Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential. o Female patients who are not surgically sterile or postmenopausal must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study. o Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy"}

Exclusion criteria

• {"criterion_text":"- Richter's transformation confirmed by biopsy\n- History of other malignancy that could affect compliance with the protocol or interpretation of results o Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible. o Patients with a malignancy that has been treated with surgery alone with curative intent will be included. Individuals in documented remission without treatment for (> / =) 2 years prior to enrollment may be included at the discretion of the investigator.\n- Uncontrolled active systemic infection (viral, bacterial, and fungal)\n- Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test from respiratory tract specimen (e.g. nasopharyngeal swab)\n- Known positive serology for human immunodeficiency virus (HIV), due to potential drug-drug interactions between anti-retroviral medications and the study drugs\n- Active hepatitis C, defined by the detectable hepatitis C ribonucleic acid (RNA) in plasma by polymerase chain reaction (PCR)\n- Patient is pregnant or breast-feeding\n- Malabsorption syndrome or other condition that precludes enteral route of administration\n- An individual organ/system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system (note that symptoms related to CLL should not be included in the patient’s screening CIRS score). Investigators should consult the General Rules for Severity Rating as well as the Organ-Specific Categories when assigning scores for certain conditions (i.e., pulmonary embolism) and consider the level of morbidity associated with a patient’s condition\n- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study\n- Patients who have received strong and moderate CYP3A inhibitors and/or CYP3A inducers within 7 days prior to the first dose of venetoclax, patients who consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax\n- Patients who require use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin). Patients may be eligible if able to be taken off warfarin and started on an alternative anticoagulant\n- Patients with evidence of any of the following conditions: o New York Heart Association Functional Classification III or IV congestive heart failure o History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration o Recent infection requiring systemic treatment; need to have completed anti-biotic therapy > 14 days before the first dose of study drug o Cerebral vascular accident or intracranial bleed within the last 6 months o Known active chronic hepatitis C o Positive serology for hepatitis B defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of hepatitis B surface antibody [HBsAb] status), a hepatitis B deoxyribonucleic acid (DNA) test will be performed and, if positive the subject will be ineligible; if the hepatitis B DNA test is negative (i.e. viral load undetectable) then the individual is eligible; if a patient who is HBsAg negative, HBcAb positive, and hepatitis B DNA negative is enrolled, they should be considered for either prophylactic anti-viral therapy or careful monitoring for HBV reactivation. Patients who have protective titers of HBsAb after vaccination or prior but cured hepatitis B are eligible."}

Primary endpoints

• {"endpoint_text":"- The proportion of patients who will achieve a CR or CRi with bone marrow MRD assessed by flow cytometry less than 10-4 at the end of treatment.","definition_or_measurement_approach":"Bone marrow MRD assessed by flow cytometry; undetectable MRD defined as <10-4 at the end of treatment."}

Secondary endpoints

• {"endpoint_text":"- Overall Response Rate (ORR) Percentage of Participants with Best Overall Response (ORR)(defined as complete response [CR], CR [CRi], nodular partial response [nPR], PR) as assessed by investigator determined using iwCLL guidelines","definition_or_measurement_approach":"ORR defined as CR, CRi, nPR, PR assessed by investigator using iwCLL guidelines."}
• {"endpoint_text":"- Percentage of participants with MRD less than 10-4 in peripheral blood at 12 months following end of treatment","definition_or_measurement_approach":"Peripheral blood MRD < 10-4 measured at 12 months after end of treatment."}
• {"endpoint_text":"- Duration of Responses (DOR) [time frame: response up to disease progression or death, whichever occurs first (up to approximately 5 years)].","definition_or_measurement_approach":"Time from response until disease progression or death, up to ~5 years."}
• {"endpoint_text":"- Progression-Free Survival (PFS) [ time frame: baseline up to disease progression or death, whichever occurs first (up to approximately 5 years)] Investigator-Assessed Progression-Free Survival (PFS) determined using standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines","definition_or_measurement_approach":"Investigator-assessed PFS using iwCLL guidelines from baseline to progression or death (up to ~5 years)."}
• {"endpoint_text":"- Overall Survival (OS) [time Frame: Baseline up to death (up to approximately 5 years)]","definition_or_measurement_approach":"Time from baseline to death from any cause (up to ~5 years)."}
• {"endpoint_text":"- Time to Next Anti-CLL Treatment (TTNT) [time frame: baseline up to next treatment or death from any cause, whichever occurs first (up to approximately 5 years)]","definition_or_measurement_approach":"Time from baseline to next anti-CLL treatment or death (up to ~5 years)."}
• {"endpoint_text":"- Quality of life (QOL) of subjects during therapy. Changes from baseline in QOL measures assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).","definition_or_measurement_approach":"QOL measured using EORTC QLQ-C30; changes from baseline assessed during therapy."}
• {"endpoint_text":"- Evaluation of safety of VR treatment comprising all grades adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v.5.0).","definition_or_measurement_approach":"Safety assessed by incidence and severity of adverse events graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- To develop innovative, machine-learning-based algorithms to assess the prediction of response to VR treatment in CLL (as a probability of selected categories of response supported by rationale) based on patients’ electronic health records.","definition_or_measurement_approach":"Exploratory development of ML algorithms using patients' electronic health records to predict response probabilities."}
• {"endpoint_text":"- To identify gut microbiota associated biomarkers that predict risk of development treatment-related toxicities (mainly infections) and kinetics and depth of response including undetectable MRD.","definition_or_measurement_approach":"Exploratory identification of gut microbiota biomarkers associated with toxicity risk and response kinetics/depth (including MRD)."}

Poland

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

02-12-2024

Processing Time Days

46

Number Of Sites

10

Number Of Participants

103

Primary sponsor

Full Name

Polish Adult Leukemia Group

Organisation Type

Patient organisation/association

Country Of Registered Address

Poland

Third parties

• {"country":"Poland","full_name":"Kapadi Sp. z o.o.","duties_or_roles":"1,10,11,12,6,7,8","organisation_type":"Pharmaceutical company"}