EUCTR2019-001573-89-FI进行中（未招募）1 期
A Phase 3b, Multicenter, Open-Label, Single-Arm Study of Acalabrutinib (ACP-196) in Subjects with Chronic Lymphocytic Leukemia
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 540
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Men and women =18 years of age (or the legal age of consent in the
- •jurisdiction in which the study is taking place).
- •2. Diagnosis of CLL that meets all published diagnostic criteria as stated
- •a. Monoclonal B-cells (either kappa or lambda light chain restricted)
- •that are clonally co-expressing =1 B-cell marker (CD19, CD20, and
- •CD23) and CD5 during screening
- •b. Prolymphocytes may comprise <55% of blood lymphocytes during
- •c. Presence of =5 × 10^9 B lymphocytes/L (5000/µL) in the peripheral
- •blood (at any point since the initial diagnosis)
- •3. Active disease per at least 1 of the following iwCLL 2018 criteria:
- •a. Evidence of progressive marrow failure as manifested by the
- •development of, or worsening of, anemia (hemoglobin <10 g/dL) and/or
- •thrombocytopenia (platelets <100,000/µL)
- •b. Massive (ie, =6 cm below the left costal margin), progressive, or
- •symptomatic splenomegaly
- •c. Massive nodes (ie, =10 cm in the longest diameter), progressive, or
- •symptomatic lymphadenopathy
- •d. Progressive lymphocytosis with an increase of >50% over a 2-month
- •period or a lymphocyte doubling time (LDT) of <6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte count obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of <30x10^9/L (30,000/µL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded
- •e. Autoimmune anemia and/or thrombocytopenia that is poorly
- •responsive to standard therapy
- •f. B-symptoms documented in the subject's chart with supportive
- •objective measures, as appropriate, defined as =1 of the following
- •disease-related symptoms or signs (please refer to protocol for related
- •4. Must meet 1 of the following criteria:
- •a. Have received no prior therapy for treatment of CLL and meets 1 of
- •the following criteria (for this study, participants in the UK will be
- •enrolled ONLY in the R/R or the prior ibrutinib cohort):
- •i. A score of >6 on the Cumulative Illness Rating Scale (CIRS)
- •ii. Creatinine clearance of 30 to 69 ml/min using the Cockcroft-Gault
- •b. Have previously received therapy for CLL and have either refractory
- •or relapsed CLL
- •c. Have received prior ibrutinib therapy (ie, defined as a subject who
- •discontinued ibrutinib for any reason prior to disease progression) for
- •CLL (please refer to protocol for definition of ibrutinib intolerance)
- •5. ECOG performance status of =2.
- •6. Female subjects of childbearing potential (ie, not surgically sterile or
- •post-menopausal) who are sexually active with a non-sterilized male
- •partner must use =1 highly effective method of contraception from the
- •time of screening and must agree to continue using such precautions for
- •2 days after the last dose of study treatment. Contraception measures
- •and restrictions on sperm donation are not required for male subjects.
- •7. Fluorescence in situ hybridization (FISH) for which the next-
- •generation sequencing (NGS) method is preferred) within 60 days during
- •screening up to before the first dose reflecting the presence or absence
- •of del(17p), 13q del, 11q del, and trisomy of chromosome 12 along with
- •the percentage of cells with the deletion, along with TP53 sequencing.
- •Subjects must also have molecular analysis to detect IGHV mutation
- •status (NGS is the preferred method) at screening if not done any tim
排除标准
- •1. Subjects who have had disease progression while on a BTKi for any
- •malignant or non-malignant condition.
- •2. Prior malignancy (other than CLL), except for adequately treated
- •basal cell or squamous cell skin cancer, in situ cancer, early-stage
- •prostate cancer, or other cancer from which the subject has been
- •disease-free for =2 years.
- •3. History of confirmed progressive multifocal leukoencephalopathy.
- •4. Significant cardiovascular disease such as symptomatic arrhythmias,
- •congestive heart failure, or myocardial infarction within 6 months before
- •screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval using Fridericia's formula (QTcF) >480 msec at screening. Note: Subjects with rate-controlled, asymptomatic atrial fibrillation are allowed to enroll in the study (For prior ibrutinib therapy cohort only), except in Finland, where this is applicable to all 3 cohorts.
- •5. Malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- •6. Evidence of active Richter's transformation. If Richter's
- •transformation is suspected (ie, lactate dehydrogenase [LDH] increased,
- •asymmetric fast lymph node growth or clinical suspicion), it should be
- •ruled out with positron emission tomography-computed tomography
- •(PET-CT) and/or biopsy according to guidelines.
- •7. Central nervous system involvement by CLL.
- •8. Known history of human immunodeficiency virus, serologic status
- •reflecting active hepatitis B virus or hepatitis C virus infection, any
- •uncontrolled active systemic infection along with subjects who are on
- •ongoing anti-infective treatment and subjects who have received
- •vaccination with a live attenuated vaccine within 4 weeks before the first
- •dose of study treatment.
- •a. Subjects who are hepatitis B core antibody (anti-HBc) positive and
- •who are hepatitis B surface antibody (anti-HBs) negative will need to
- •have a negative hepatitis B virus PCR result before enrollment. Those
- •who are hepatitis B surface antigen (HBsAg) positive or hepatitis B virus
- •PCR positive will be excluded.
- •b. Subjects who are hepatitis C virus antibody positive will need to have
- •a negative hepatitis C virus PCR result before enrollment. Those who are
- •hepatitis C virus PCR positive will be excluded.
- •9. Uncontrolled autoimmune hemolytic anemia or idiopathic
- •thrombocytopenic purpura defined as declining hemoglobin or platelet
- •count secondary to autoimmune destruction within the screening period
- •or requirement for high doses of steroids (>20 mg daily of prednisone or
- •equivalent for longer than 2 weeks).
- •10. History of stroke or intracranial hemorrhage within 6 months before
- •the first dose of study treatment.
- •11. History of bleeding diathesis (eg, hemophilia or von Willebrand
- •12. Presence of a GI ulcer diagnosed by endoscopy within 3 months
- •before screening.
- •13. Major surgical procedure within 4 weeks before first dose of study
- •treatment. Note: Subjects who have had major surgery must have
- •recovered adequately from any
- •toxicity and/or complications from the intervention before the first dose
- •of study treatment.
- •14. Requires treatment with proton-pump inhibitors (eg, omeprazole,
- •esomeprazole, lansoprazole, dexlansoprazole, rabeprazo
研究者
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