Addition of ritonavir to ibrutinib treatment in patients with chronic leukemia and certain types of lymphoma

Prior treatment

• Diagnosis of any previous or concomitant malignancy: – except when the patient successfully completed treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for this malignancy at least 24 months prior to registration, – except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix,
• Current concomitant chemotherapy, radiation therapy, or immunotherapy
• Participation in another interventional clinical study at the time of inclusion or during protocol treatment without prior approval
• Essential use of strong inhibitors or inducers of Cytochrome P450 3A (CYP3A), Cytochrome P450 2D6 (CYP2D6), Uridine Diphosphate glucuronosyltransferase (UGT) or P glycoprotein (P gp) or substrates of the aforementioned enzymes with a narrow therapeutic window
• Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled: infection, autoimmune hemolysis, immune thrombocytopenia, diabetes, hypertension, hyperthyroidism or hypothyroidism etc.)
• Ongoing active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to Cycle 1 Day 1 (C1D1)
• History of stroke or intracranial hemorrhage within 6 months prior to registration

Other illness

• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Intolerability, contra-indication or allergy to one of the study drugs
• Cardiac dysfunction as defined by: – Myocardial infarction within the last 3 months of study registration, – Heart failure (NYHA) grade IV), – Unstable cardiac arrhythmias
• History of non-compliance to medical regimens or considered unreliable with respect to compliance
• Senile dementia, mental impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent

Age

• Fertile men or women of childbearing potential (WOCBP) unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method during study treatment and until 3 months after ibrutinib treatment

Other

• Symptomatic central nervous system (CNS) involvement

• ≥ 18 years
• Patients with a diagnosis of chronic lymphocytic leukemia (CLL), lymphoplasmacytic lymphoma (LPL) or mantle cell lymphoma (MCL) according to the World Health Organization classification (WHO 2024)
• Patients receiving ibrutinib > 60 days at the time of inclusion without any dose-reduction
• World Health Organization performance status (WHO PS) 0, 1 or 2
• Adequate renal and hepatic functions as indicated by the laboratory values described in the protocol unless clearly disease related
• Patient is able and willing to adhere to the study visit schedule and other protocol requirements
• Patient is capable of giving informed consent
• Written informed consent