Ibrutinib Adapted to Response in Patients Diagnosed With Chronic Lymphatic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 主要终点
- Evaluate Progression Free Survival (PFS) in patients diagnosed with Chronic Lymphocytic Leukemia who undergo the treatment scheme protocolized by GATLA.
研究概览
简要总结
As everyone knows in clinical practice, Ibrutinib dose reduction in patients with CLL with good response does not alter disease-free survival (DFS) or increase the risk of transformation.
Supported by the evidence of retrospective studies that have shown parity in DFS and OS between a group with standard treatment and another in which the dose of ibrutinib was reduced and others in which no significant differences were observed in the saturation point of the BTK receptor with good clinical response, even comparing plasma and intracellular pharmacokinetics and BTK occupancy together with the pharmacodynamic response, we propose to carry out a prospective response-adapted study with the aim of potentially reducing the rate of adverse events and improving the cost/benefit ratio of this therapy. Evaluating the efficacy and safety of Ibrutinib dose appropriate to the response in patients diagnosed with CLL.
详细描述
Chronic lymphatic leukemia is the most common form of leukemia in adults, most often arising from a malignant clone of B cells with a characteristic phenotype. It is far from uniform in presentation and clinical course. About a third of patients never require treatment and have a long survival; in another third, an initial indolent phase is followed by disease progression; the remaining third of patients have aggressive disease at onset and require immediate treatment.
The development of the Rai and Binet staging systems has allowed the division of patients with chronic lymphocytic leukemia into three prognostic groups: good, intermediate and poor prognosis.
The two staging systems have improved the identification of patients who need immediate treatment.
In recent years, a variety of new kinase inhibitors have been designed that target various components of the BCR signaling pathway. Targets primarily include phosphatidylinositol 3'kinase (PI3K) and Bruton's tyrosine kinase (BTK). All of these new drugs share a response pattern that results in nodal reduction and increased lymphocytosis, reflecting modulation of the microenvironment, which could prevent these cells from receiving survival signals emitted by the microenvironment. More importantly, these drugs appear to be able to bypass p53 deletion, raising the possibility that they may target existing proliferative pools in the bone marrow and lymph nodes, thus bringing therapy closer to curing p53. disease.
The treatment of chronic lymphatic leukemia (CLL) represents the paradigm of advances in the therapy of hematological neoplasms. In its beginnings, CLL therapy used monodrugs that gradually led to their combination in duplets and triplets with which results never before obtained were achieved. The development of Ibrutinib was probably the milestone that marked the importance of the signaling pathways of leukemic cells in the progression of the disease, opening the investigation of new target drugs that constitute the basis of current treatment in CLL.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with CLL with criteria for starting treatment.
- •Patients diagnosed with relapsed/refractory CLL.
- •Patients diagnosed with CLL not exposed to iBTK.
- •Patients with a diagnosis of CLL older than 18 years.
- •Patients who have been diagnosed within the six months prior to the start of the registry will also be eligible, if they are followed prospectively by the participating centers and the required information is available.
- •Signature of the informed consent.
- •Patients who understand the risk of pregnancy during treatment and are willing to use safe contraceptive methods.
排除标准
- •CLL without criteria for starting treatment.
- •Small cell lymphocytic lymphoma.
- •Previous exposure to iBTK.
- •HIV positive, hepatitis B or C positive (unless there is vaccination), Chagas positive or HTLV-1 positive.
- •Performance Status (ECOG) >=
- •Second active malignancy currently requiring treatment (with the exception of basal cell carcinoma).
- •Class III or IV heart failure, previous acute myocardial infarction, unstable angina, ventricular tachyarrhythmias requiring treatment, severe COPD with hypoxemia, uncontrolled DBT or uncontrolled hypertension, active gastric ulcer.
- •Active viral, bacterial, or fungal infection.
- •Impaired renal function with clearance < 40 mL/min.
- •BT/BD, GOT/GPT x
- •Mental deficiency that prevents adequate understanding of the treatment requirements.
- •Thrombocytopenia (<30,000).
- •Use of oral anticoagulants.
- •Pregnancy / Lactation.
结局指标
主要结局
Evaluate Progression Free Survival (PFS) in patients diagnosed with Chronic Lymphocytic Leukemia who undergo the treatment scheme protocolized by GATLA.
时间窗: 24 months
Determine duration of response with dose reduction.
时间窗: 24 months
Determine global response rate with dose reduction.
时间窗: 24 months
次要结局
- Evaluate Overall Survival (OS) in patients diagnosed with Chronic Lymphocytic Leukemia who undergo the treatment scheme protocolized by GATLA.(24 months)
- Assess rate of adverse events grade 3 or more.(24 months)