Ibrutinib, Obinutuzumab and Venetoclax for Patients With Chronic Lymphocytic Leukemia

• Status: Completed
• Trial end date: 2021-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Background: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in the occidental countries. Until now, it is considered a chronic disease without a cure. The development of new molecular therapies have showed that the cure may be an option. This protocol propose a triple sequential therapy with three direct therapies for the leukemic cell: an inhibitor of Bruton´s tyrosine kinase (ibrutinib), a second generation monoclonal antibody versus CD20 (obinutuzumab) and a BCL-2 inhibitor (venetoclax) as treatment of first or second line in CLL.

Objective: Negativize the minimal residual disease and by this way obtain longer survivals (overall survival and relapse free survival).

Design: This is a multicenter, longitudinal, experimental, open, non-randomized and non-comparable study coordinated by the "Grupo Cooperativo de Hemopatías Malignas" situated on Hospital Angeles Lomas in Huixquilucan, México. The study, is a phase II clinical study that will employ three target therapy drugs in sequencing phases. It will start with a BTK inhibitor as induction, later an anti-CD20 will be used for consolidation and it will end with a BH3 analog as maintenance for one year. The primary outcome is the negativization of minimal residual disease.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Grupo Cooperativo de Hemopatías Malignas
• Treatments: Obinutuzumab; Venetoclax

Criteria

Inclusion Criteria:

• Patients diagnosed with B cell chronic lymphocytic leukemia according to 2017 WHO criteria by immunophenotype/immunohistochemistry with active disease according to the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and do not present TP53 mutation and/or del(17)p. (Cohort 1).

• Patients diagnosed with relapsed/refractory chronic lymphocytic leukemia that have previously received at least one line of treatment that does not include the drugs in the study scheme. (Cohort 2).

• Functional stage of 0 - 2 measured by the Eastern Cooperative Oncology Group (ECOG) scale.

• Creatinine depuration ≥ 30 ml/min measured in a 24-hour urine recollection or utilizing the CKD-EPI formula.

• Proper liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN in patients with Gilbert syndrome, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN.

• Capacity and willingness to provide a written informed consent.

Exclusion Criteria:

• T cell lymphocytic leukemia diagnosis.

• TP53 mutation and/or del(17)p presence.

• Non-controlled systematic active infection (viral, bacterial and/or fungic).

• Patients with known infection by human immunodeficiency virus (HIV).

• Active infection by hepatitis B (defined as the presence of detectable HBV's DNA, HBe antigen or HBs antigen). Patients with serological evidence of previous vaccination (HBsAg negative, anti-HBs positive antibodies, anti-HBc negative antibodies) are eligible. The patients that are HBsAg negative/ anti-Hbs positive antibodies but anti-HBc positive antibodies are eligible, if the HBV DNA is negative, and the HBV-DNA PCR is realized every 12 months after the last cycle of treatment.

• Active infection by hepatitis C, defined by the ribonucleic acid (RNA) of hepatitis C is detectable in plasma by polymerase chain reaction (PCR).

• Significant cardiovascular diseases such as uncontrolled or symptomatic arrhythmias, congestive heart failure or acute myocardial infarction within 2 months prior to screening, or any class 3 or 4 heart disease according to the functional classification of the NYHA.

• Diagnosis of previous malignancies for 2 years, with exception of patients with basal or squamous cell carcinoma or "in situ" carcinoma of cervix or breast.

• Requiring therapy with inhibitors or potent inducers of CYP3A4 and CYP3A5 inhibitors.

• Anticoagulant therapy with acenocoumarol or warfarin.

• History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to screening.

• History of allergic reaction or severe anaphylaxis to humanized or murine monoclonal antibodies.

• Pregnant or lactating women.