Main info

Identificatie:

HOVON 185 BKTi

Sponsor:

HOVON

Working group party:

Lymphoma

Included patients:

0

(of 170)

Active sites:

0

(of 25)

25 sites are pending

Title:

Bioequivalence of ritonavir boosted ibrutinib in patients with chronic lymphocytic leukemia, lymphoplasmacytic- and mantle cell lymphoma

Timeline

Details

Phase:

Prospective Phase II study

Monitoring Type:

Objectives:

Primary study objective (run-in phase)

• To demonstrate that ritonavir-boosted low-dose ibrutinib provides adequate systemic exposure relative to standard-dose ibrutinib.

Primary study objective (extension phase)

• To assess the toxicity of a defined schedule of ritonavir added to ibrutinib in adult patients with CLL, LPL, and MCL.

Secondary study objectives (run-in phase)

• To assess ibrutinib and ritonavir CL, Cmax, Tmax, Cmin.
• To assess the impact of ritonavir boosted ibrutinib on QoL.

Secondary study objectives (extension phase)

• To assess ibrutinib and ritonavir CL, Cmax, Tmax, Cmin, AUC0-24 based on an optimized sampling schedule.
• To assess the feasibility of a defined schedule of ritonavir boosted ibrutinib in adult patients with CLL, LPL, and MCL.
• ORR at week 52.
• To report PFS and OS of patients treated with ritonavir boosted ibrutinib.
• To assess the exposure-toxicity and exposure-response relation of ibrutinib.
• To assess the impact of ritonavir boosted ibrutinib on QoL.
• To assess cost-savings on ibrutinib drug costs (corrected for ritonavir costs) compared to the standard dosing schedule.

Exploratory objectives

• To assess the impact of pharmacogenetic factors on ibrutinib exposure.
• To compare outcome of patients treated with ibrutinib-ritonavir to historical data or a matched cohort of the NCR.

Eligibility

Inclusion Criteria:

• ≥ 18 years
• Patients with a diagnosis of CLL, LPL or MCL according to the World Health Organization (WHO)-2024 classification (see Appendix A).
• Patients receiving ibrutinib > 60 days at the time of inclusion without any dose-reduction.
• WHO performance status 0, 1 or 2 (see Appendix B).
• Adequate renal and hepatic functions as indicated by the laboratory values below unless clearly disease related:
  • Adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; either calculated by the eGFR formula or measured by 24 hours urine collection.
  • Serum bilirubin ≤ 3 x upper limit of normal (ULN), unless due to Gilbert’s syndrome.
  • Alanine transaminase (ALT) ≤ 3 x ULN
• 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.

Exclusion Criteria:

• 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.
• 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 C1D1.
• Cardiac dysfunction as defined by:
  • Myocardial infarction within the last 3 months of study registration, or
  • Heart failure (New York Heart Association (NYHA) grade IV), or
  • Unstable cardiac arrhythmias.
• History of stroke or intracranial hemorrhage within 6 months prior to registration.
• Symptomatic central nervous system (CNS) involvement.
• 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.
• Fertile men or women of childbearing potential unless: (1) surgically sterile or ≥ 2 years after the onset of menopause; (2) willing to use a highly effective contraceptive method such as oral contraceptives, intrauterine device, sexual abstinence or combination of male condom with either cap, diaphragm, or sponge with spermicide (double barrier methods) during study treatment and until 3 months after ibrutinib treatment.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals