A prospective, multi-centre, phase IV clinical trial to assess the safety and efficacy of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia and relapsed and refractory mantle cell lymphoma
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 15
- 主要终点
- R/R CLL/ SLL, and relapsed & refractory
研究概览
简要总结
This is a phase IV, open-label, single-arm,multi-centre, prospective study.
The study is plans to assess the safety andefficacy of Acalabrutinib 100 mg capsule in Indian patients. The data obtainedfrom the study will help to understand the safety and efficacy profile ofAcalabrutinib in Indian patients with chronic lymphocyticleukaemia (CLL) / Small LymphocyticLymphoma (SLL), and patients with Mantle Cell Lymphoma (MCL) who have receivedat least one prior therapy.
The Treatment Phase will be from the start of Cycle1, Day 1 to end of Cycle 6, Day 28, or until study drug discontinuation due toeither disease progression or unacceptable toxicity or other reasons whicheveroccurs earlier. Each cycle of treatment is 28 days.
Patientswill be monitored throughout the study period for AdverseEvents (AEs) / Serious Adverse Events (SAEs) of Acalabrutinib. Allpatients who receive Acalabrutinib capsule 100 mg BID will be evaluated forefficacy once every 03 months during the treatment phase. Safety evaluationswill include clinical laboratory parameters (haematology and biochemistry),physical examinations, vital sign measurements, ECG monitoring, ECOGperformance status and adverse event monitoring.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Men and Women aged 18yrs or more.
- •2.Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2 3.Able to receive all outpatient treatments, all laboratory monitoring, and all radiologic evaluations.
- •4.The following laboratory parameters: a.Absolute neutrophil count (ANC) ≥750 cells/μL or ≥500 cells/μL in patients with documented bone marrow involvement, and independent of growth factor support 07 days before the assessment b.Platelet count ≥50,000 cells/μL or ≥30,000 cells/μL in patients with documented bone marrow involvement, and without transfusion support 07 days before the assessment c.Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.0 x ULN d.Total bilirubin ≤1.5 x ULN e.Estimated creatinine clearance of ≥30 mL/min 5.Refractory disease defined as achieving less than partial response with the most recent treatment within 6 months before study entry 6.Provision of signed, written and dated informed consent prior to any study-specific Procedures.
- •7.The patients of either CLL or MCL: a.CLL patients: i.
- •Treatment naïve or ≥1 prior systemic therapy for CLL ii.
- •Diagnosis of CD20+ CLL that meets published diagnostic criteria (Hallek et al.
- •An active disease that meets ≥1 of the following iwCLL 2018 criteria for requiring treatment: 1) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia.
- •Cut-off levels of Hb <10 g/dL or platelet counts <100 × 109/L are generally regarded as an indication for treatment.
- •However, in some patients, platelet counts <100 × 109/L may remain stable over a long period; this situation does not automatically require therapeutic intervention.
- •Massive (i.e., ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
- •Massive nodes (i.e., ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
- •Progressive lymphocytosis with an increase of ≥50% over a 2-month period or Lymphocyte Doubling Time (LDT) in <6 months.
- •LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; patients with initial blood lymphocyte counts <30 × 109/L may require a longer observation period to determine the LDT.
- •Factors contributing to lymphocytosis other than CLL (e.g., infections, steroid administration) should be excluded.
- •Autoimmune complications, including anaemia or thrombocytopenia poorly responsive to corticosteroids.
- •Symptomatic or functional extra-nodal involvement (e.g., skin, kidney, lung, spine).
- •Disease-related symptoms as defined by any of the following: a) Unintentional weight loss of ≥10% within the previous 06 months.
- •b) Significant fatigue (i.e., ECOG performance scale 02 or worse; cannot work or unable to perform usual activities).
- •d) Night sweats for ≥1 month without evidence of infection.
- •b.MCL Patients: i.
- •Confirmed MCL with translocation t(11;14) (q13;q32) and/or overexpressed cyclin D1 ii.
- •Measurable nodal disease (one or more lesions measuring ≥2 cm in the longest diameter) iii.
- •Relapsed after, or were refractory to, 1-5 previous treatments.
排除标准
- •1.Known prolymphocytic leukaemia, Central Nervous System (CNS) lymphoma or leukaemia; or known history of (or currently suspected) Richter’s syndrome 2.Treatment with chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days of the first dose of study drug 3.Prior radio-conjugated or toxin-conjugated antibody therapy 4.Anticoagulation therapy (e.g., warfarin or equivalent vitamin K antagonists) within 07 days of the first dose of study drug.
- •5.Major surgery ≤30 days before the first dose of study drug 6.History of stroke or intracranial haemorrhage ≤6 months before the first dose of study drug 7.History of bleeding diathesis 8.Prior exposure to a B-cell lymphoma-2 (Bcl-2) inhibitor or B-cell receptor inhibitor like BTKs 9.Active Cytomegalovirus (CMV) infection or serologic status reflecting active Hepatitis B or C infection or known history of infection with Human Immunodeficiency Virus (HIV), or any uncontrolled active systemic infection.
- •10.Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, Congestive Heart Failure, or Myocardial Infarction within 06 months of screening, or any Class 3 or 4 cardiac diseases as defined by the New York Heart Association Functional Classification, or QTcB >480 msec at screening.
- •11.Requiring treatment with proton-pump inhibitors (e.g., Omeprazole, Esomeprazole, Lansoprazole, Dexlansoprazole, Rabeprazole, or Pantoprazole).
- •12.Breastfeeding or pregnant.
- •13.Current life-threatening illness, medical condition, or organ/system dysfunction which, in the Investigator’s opinion, could have compromised the subject’s safety or put the study at risk.
- •14.Concurrent participation in another therapeutic clinical trial.
结局指标
主要结局
R/R CLL/ SLL, and relapsed & refractory
时间窗: Screening visit to 28 days after the last Acalabrutinib dose in the treatment phase.
MCL in Indian patients
时间窗: Screening visit to 28 days after the last Acalabrutinib dose in the treatment phase.
To investigate the safety of Acalabrutinib
时间窗: Screening visit to 28 days after the last Acalabrutinib dose in the treatment phase.
among patients with treatment naïve and
时间窗: Screening visit to 28 days after the last Acalabrutinib dose in the treatment phase.
次要结局
- To assess the efficacy of Acalabrutinib in(patients of CLL/SLL and relapsed &)