IBRUTINIB for Chronic lymphocytic leukemia | Small lymphocytic lymphoma | Monoclonal B-cell lymphocytosis (CLL-like)

Inclusion criteria

• {"criterion_text":"- Diagnosis of CLL/small lymphocytic lymphoma (SLL) or CLL-like monoclonal B-cell lymphocytosis (MBL) according to IWCLL guidelines"}
• {"criterion_text":"- Willingness of men and WOCBP, and their partners, to observe the contraceptive measures until the end of systemic exposure"}
• {"criterion_text":"- Willingness of men not to father a child or donate sperm while receiving ibrutinib, and for 3 months following completion of treatment"}
• {"criterion_text":"- Patients >18 years old"}
• {"criterion_text":"- Active AIHA (warm AIHA, wAIHA, or cold hemagglutinin disease, CAD) that i) is relapsed after previous treatment with corticosteroids (with or without rituximab), or ii) is steroid-resistant (failure to obtain hematologic response within 3 weeks on at least 1 mg/kg predniso(lo)ne (2)), or iii) is steroid-dependent (need to continue on predniso (lo)ne at a dose of >10 mg/day to maintain a response (2)). AIHA is defined as: anemia (hemoglobin =10 g/dL; or hemoglobin >10 g/dL dependent on transfusions to maintain this level of hemoglobin) and laboratory evidence of hemolysis (presence of 3 of 4 markers: increased reticulocyte count, increased indirect bilirubin, increased lactate dehydrogenase, decreased haptoglobin) and positive DAT (either IgG DAT, C3 DAT or both)."}
• {"criterion_text":"- Eligibility of patients with DAT-negative active AIHA should be confirmed by the Principal Investigator and co-Principal Investigator for the trial"}
• {"criterion_text":"- Signed written informed consent according to ICH/EU/GCP and national local laws"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) =2"}
• {"criterion_text":"- Adequate renal and hepatic function, per laboratory reference range at screening as follows: o Aspartate aminotransferase (AST) =< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy) o Alanine aminotransferase (ALT) =< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy) o Creatinine clearance of >= 30 mL/min per 24-hour urine test or the Cockcroft-Gault formula (within 30 days prior to day 1 of protocol therapy)"}
• {"criterion_text":"- Ability to swallow oral study medication"}
• {"criterion_text":"- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test within the screening window prior to receiving the first dose of study medication and monthly pregnancy test until the end of systemic exposure"}

Exclusion criteria

• {"criterion_text":"- Contraindication to ibrutinib therapy as per treating physician’s discretion."}
• {"criterion_text":"- Contraindication to ibrutinib therapy as per ibrutinib data sheet (severe hepatic impairment, known allergy to the drug or to one of the excipients, concomitant treatment with warfarin or other vitamin K antagonists)"}
• {"criterion_text":"- Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) or known positive human immunodeficiency virus (HIV) o Participants who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. o Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded o Subjects who have an undetectable or unquantifiable HIV viral load with CD4 > 300 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures - Previous exposure to ibrutinib as CLL-directed therapy"}
• {"criterion_text":"- Previous exposure to ibrutinib as CLL-directed therapy"}
• {"criterion_text":"- Treatment with another investigational drug or device, or approved therapy for investigational use – with the exception of corticosteroids - 28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer"}
• {"criterion_text":"- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the oral-administered study treatments"}
• {"criterion_text":"- Vaccination with a live vaccine within 28 days prior to Cycle 1 Day 1"}
• {"criterion_text":"- Female patients who are currently in pregnancy or are willing to be pregnant or are lactating."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of this study is to assess AIHA ORR after 6 cycles of therapy (28-day cycles).","definition_or_measurement_approach":"AIHA Overall Response Rate (ORR) assessed after 6 cycles (28-day cycles)."}

Secondary endpoints

• {"endpoint_text":"- AIHA ORR after 3 and 12 cycles of therapy (28-day cycles).","definition_or_measurement_approach":"AIHA Overall Response Rate assessed after 3 and 12 cycles (28-day cycles)."}
• {"endpoint_text":"- AIHA response duration (measured from the achievement of CR or PR to the loss of response).","definition_or_measurement_approach":"Duration measured from achievement of CR or PR to loss of response."}
• {"endpoint_text":"- AIHA-specific relapse-free survival (RFS).","definition_or_measurement_approach":"Relapse-free survival specific to AIHA as defined in protocol."}
• {"endpoint_text":"- Frequency of packed red blood cell (PRBC) transfusion while receiving ibrutinib.","definition_or_measurement_approach":"Count/frequency of PRBC transfusions during ibrutinib treatment."}
• {"endpoint_text":"- Rate of patients needing further AIHA-directed treatment during ibrutinib therapy.","definition_or_measurement_approach":"Proportion of patients requiring additional AIHA-directed therapies during ibrutinib treatment."}
• {"endpoint_text":"- Incidence and type of treatment-related toxicity.","definition_or_measurement_approach":"Recording of incidence and type of adverse events/toxicities related to treatment."}
• {"endpoint_text":"- CLL ORR, PR and CR rate after 3, 6 and 12 cycles of therapy (28-day cycles). CLL response is defined according to IWCLL guidelines (1).","definition_or_measurement_approach":"CLL responses (ORR, PR, CR) measured after 3, 6, and 12 cycles per IWCLL guidelines."}
• {"endpoint_text":"- Duration of CLL response.","definition_or_measurement_approach":"Duration measured from response to progression/loss of response for CLL."}
• {"endpoint_text":"- CLL-specific EFS.","definition_or_measurement_approach":"Event-free survival specific to CLL as defined in protocol."}
• {"endpoint_text":"- CLL-specific PFS.","definition_or_measurement_approach":"Progression-free survival specific to CLL as defined in protocol."}
• {"endpoint_text":"- Overall OS. OS will be evaluated both in the entire cohort and in the CLL/SLL cohort (excluding patients with CLL-like MBL).","definition_or_measurement_approach":"Overall survival evaluated in entire cohort and separately in CLL/SLL cohort (excluding CLL-like MBL)."}
• {"endpoint_text":"- Quality of Life at baseline and after 3, 6 and 12 cycles of therapy (28-day cycles)","definition_or_measurement_approach":"Quality of life assessments at baseline and after 3, 6 and 12 cycles (instruments not specified here)."}
• {"endpoint_text":"- Number and percentage of T-cell subsets in peripheral blood at baseline and after 6 and 12cycles of therapy (28-day cycles).","definition_or_measurement_approach":"Quantitative counts and percentages of peripheral blood T-cell subsets at baseline and after cycles 6 and 12."}
• {"endpoint_text":"- Percentage of T cells expressing activation markers and checkpoint molecules at baseline and after 6 and 12 cycles of therapy (28-day cycles).","definition_or_measurement_approach":"Flow cytometry assessment of activation and checkpoint marker expression on T cells at baseline and after cycles 6 and 12."}
• {"endpoint_text":"- Serum concentration of T-cell related cytokines at baseline and after 6 and 12 cycles of therapy (28-day cycles).","definition_or_measurement_approach":"Measurement of serum concentrations of T-cell related cytokines at baseline and after cycles 6 and 12."}

Italy

Earliest CTIS Part Ii Submission Date

22-11-2023

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

553

Number Of Sites

23

Number Of Participants

45

Primary sponsor

Full Name

Fondazione Gimema Franco Mandelli Onlus

Organisation Type

Health care

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Laboratorio di Ematologia Traslazionale","duties_or_roles":"code: 4","organisation_type":"Health care"}