Phase 2a Study on the Efficacy of Ibrutinib and Venetoclax in MRD-Guided Treatment for Relapsed/Refractory Chronic Lymphocytic Leukemia

Trial ID: 2024-514686-19-00
Sponsor: Ospedale San Raffaele S.r.l.

Trial statistics

science

test molecule

location_city

research sites

public

country

medical_information

diseases

person_search

investigators

Diseases & Conditions

Chronic lymphocytic leukaemia Chronic lymphocytic leukaemia refractory

Objectives

The primary objective of this clinical trial is to evaluate the **efficacy** of adding ibrutinib to venetoclax in achieving minimal residual disease (MRD) negativity in patients with relapsed or refractory **Chronic Lymphocytic Leukemia (CLL)**. This is clinically relevant as MRD negativity is associated with improved patient outcomes and may indicate a deeper remission, potentially leading to longer progression-free survival in this patient population.

Participants

The clinical trial focuses on patients with **Relapsed or Refractory Chronic Lymphocytic Leukemia** (CLL). The study population includes both male and female participants, with an age range corresponding to adults and older adults. The trial does not involve a vulnerable population. Participants were selected based on specific criteria, including documented CLL requiring treatment according to the IWCLL criteria and having relapsed or refractory CLL after receiving at least one prior therapy. Adequate bone marrow function is required, with specific thresholds for absolute neutrophil count, platelet count, and hemoglobin levels. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

Plans and Procedures

The clinical trial is designed to evaluate the **efficacy** and safety of adding ibrutinib to venetoclax in patients with **relapsed or refractory chronic lymphocytic leukemia** (CLL). This is a multi-center, open-label, uncontrolled, Phase 2a trial. The primary objective is to assess the rate of minimal residual disease (MRD) negativity using multi-color flow cytometry analysis within the treatment period. The trial is expected to conclude by January 31, 2025, with recruitment having started on November 8, 2017.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as documented CLL requiring treatment and adequate bone marrow function. The treatment phase involves the administration of venetoclax, a film-coated tablet taken orally, with a maximum daily dose of 400 mg and a total dose not exceeding 260,190 mg over a maximum treatment period of 24 months. The study will include regular follow-up visits to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will evaluate the overall outcomes and MRD status.

Participant involvement is expected to last up to 24 months, depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include significant adverse reactions, disease progression, or withdrawal of consent. The trial's design does not include a control group, and the open-label nature means that both participants and investigators are aware of the treatment being administered. The trial aims to provide valuable insights into the potential benefits of combining ibrutinib with venetoclax in this patient population.

Treatment

The clinical trial involves the administration of **VENETOCLAX**, a chemical compound used in the treatment of patients with relapsed/refractory **Chronic Lymphocytic Leukemia (CLL)**. **VENETOCLAX** is provided in the form of a film-coated tablet, designed for **oral use**. The maximum daily dose of **VENETOCLAX** is 400 mg, with a total maximum dose of 260,190 mg over the course of the treatment. The treatment period is set to a maximum of 24 months. The administration of **VENETOCLAX** is monitored to ensure compliance with the dosing schedule, and adjustments are made based on the patient's response and tolerance to the medication.

In addition to **VENETOCLAX**, the study evaluates the efficacy of adding **Ibrutinib** to the treatment regimen. **Ibrutinib** is not described in detail within the provided data, but it is known to be a standard treatment for **CLL**. The trial employs a minimal residual disease (MRD)-guided approach to assess the combination's effectiveness. The study is open-label and uncontrolled, focusing on the safety and efficacy of this combination therapy. Participant compliance with the treatment regimen is closely monitored throughout the trial to ensure accurate assessment of the therapeutic outcomes.

Efficacy

The efficacy of the clinical trial will be assessed by evaluating the **minimal residual disease (MRD) negativity rate** in patients with relapsed/refractory Chronic Lymphocytic Leukemia (CLL). The primary endpoint is the MRD negativity rate, which will be determined using multi-colour flow cytometry analysis with a limit of detection of 10^-4. This assessment will be conducted within the treatment period to determine the effectiveness of adding ibrutinib to venetoclax in achieving MRD negativity. The trial is designed as a multi-center, open-label, uncontrolled, Phase 2a study, focusing on the safety and efficacy of this combination therapy in a MRD-guided approach.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

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

cancel

Exclusion Criteria

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
Previous treatment with BTK and/or BCL2 inhibitors (patients previously treated with PI3K inhibitors are eligible)
Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
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
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.