Clinical trial with Ibrutinib and Venetoclax for patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Trial details

Who runs it

Ospedale San Raffaele S.r.l.

Trial code

EU 2024-514686-19-00

Record updated

2024. augusztus 5.

Original description

To evaluate the efficacy of the addition of ibrutinib to venetoclax in terms of minimal residual disease (MRD) negativity in patients with relapsed/refractory CLLRead full original descriptionShow less

A Multi-Center, Open Label, Uncontrolled, Phase 2a Clinical Trial Evaluating the Safety and Efficacy of the Addition of Ibrutinib to Venetoclax through a MRD-guided Approach in Relapsed/Refractory Patients with Chronic Lymphocytic Leukemia (CLL) IMPROVE (Ibrutinib treatment based on MRD-guided apPROach combined with VEnetoclax)

To evaluate the efficacy of the addition of ibrutinib to venetoclax in terms of minimal residual disease (MRD) negativity in patients with relapsed/refractory CLL

Inclusion: Documented CLL requiring treatment according to the IWCLL criteria (Hallek et al. 2008); Relapsed/refractory CLL patients who received at least 1 prior therapy; Adequate bone marrow function without transfusion < 2 weeks of screening as follows: a. Absolute neutrophil count (ANC) =1.0 x 109/L (growth factors administration is allowed) b. Platelets =30 x 109/L. If thrombocytopenia due to BM involvement, platelets should be = 20 x 109/L c. Hemoglobin value =8.0 g/dl.

Exclusion: Previous treatment with BTK and/or BCL2 inhibitors (patients previously treated with PI3K inhibitors are eligible); Requires the use of warfarin, marcumar, or phenprocoumon (potential drug-drug interaction increasing exposure of warfarin or phenprocoumon): low molecular weight drugs e.g. heparin are acceptable; Treatment, administration or consumption of any of the following within 3 days prior to the first dose of venetoclax (see also Appendix G). a. Strong Cytochrome P450 3A (CYP3A) inhibitors b. Moderate CYP3A inhibitors c. Moderate or strong CYP3A inducers d. PI3K inhibitors (e.g. Idelalisib); e. Grapefruit or grapefruit products f. Seville oranges (including marmalade containing Seville oranges) g. Star fruit; Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia; Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded; History of other malignancies, except: a. Malignancy treated with curative intent and with no known active disease present for =3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c. Adequately treated carcinoma in situ without current evidence of disease; Transformation of CLL to aggressive NHL (Richter’s transformation or pro-lymphocytic leukemia); Known central nervous system (CNS) involvement; Inadequate renal function: CrCl <30 mL/min.

EU CTIS 2024-514686-19-00