2023-509359-15-00
进行中（未招募）
3 期
A Randomized, Multicenter, Open-Label, Phase 3 Study of Acalabrutinib (ACP-196) Versus Investigator’s Choice of Either Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia
概览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 25
- 试验地点
- 13
- 主要终点
- The primary endpoint of the study is PFS (defined as the time from randomization until disease progression or death from any cause) as assessed by the IRC per IWCLL 2008 criteria.
概览
简要总结
To evaluate the efficacy of acalabrutinib monotherapy (Arm A) compared with idelalisib/rituximab or bendamustine/rituximab (Arm B) based on IRC assessment of PFS per IWCLL 2008 criteria in subjects with R/R CLL.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Men and women ≥ 18 years of age.
- •Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of idelalisib, 6 months after the last dose of bendamustine, or 12 months after the last dose of rituximab, whichever is longer.
- •Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules without difficulty.
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
- •ECOG performance status of 0 to
- •Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008): a. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD
- •b. Prolymphocytes may comprise ≤ 55% of blood lymphocytes. c. Presence of ≥ 5 x 109 B lymphocytes/L (5000/µL) in the peripheral blood (at any point since initial diagnosis).
- •Must have documented CD20-positive CLL.
- •Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment: 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 (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly. c. Massive nodes (i.e., ≥ 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 LDT of < 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 x 109/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 (e.g., infections) should be excluded. e. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy. f. Constitutional symptoms documented in the subject’s chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs: i. Unintentional weight loss ≥ 10% within the previous 6 months before screening. ii. Significant fatigue (ECOG performance score 2; inability to work or perform usual activities). iii. Fevers higher than 100.5°F or 38.0°C for ≥ 2 weeks before screening without evidence of infection iv. Night sweats for > 1 month before screening without evidence of infection.
- •Meet the following laboratory parameters: a. ANC ≥ 750 cells/μL (0.75 x 109/L), or ≥ 500 cells/μL (0.50 x 109/L) in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment. b. Platelet count ≥ 50,000 cells/μL (50 x 109 /L), or ≥ 30,000 cells/μL (30 x 109/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded. If an Investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75,000 cells/μL (75 x 109/L). c. Serum AST and ALT ≤ 2.0 x ULN. d. Total bilirubin ≤ 1.5 x ULN. e. Estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female].
排除标准
- •Known CNS lymphoma or leukemia.
- •History of prior malignancy except for the following: a. Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician. b. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer. c. Adequately treated carcinoma in situ without current evidence of disease.
- •Significant cardiovascular disease such as uncontrolled or untreated symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec (calculated using Fridericia's formula: QT/RR0.33) at screening.
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- •Received a live virus vaccination within 28 days of first dose of study drug.
- •Known history of infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral, or fungal).
- •Active CMV infection (active viremia as evidenced by positive polymerase chain reaction [PCR] result for CMV DNA).
- •Serologic status reflecting active hepatitis B or C infection. a. Subjects who are anti-HBc positive and who are surface antigen negative will need to have a negative PCR result before randomization. Those who are HbsAg-positive or hepatitis B PCR positive will be excluded. b. Subjects who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
- •Ongoing, drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
- •History of or ongoing drug-induced pneumonitis.
结局指标
主要结局
The primary endpoint of the study is PFS (defined as the time from randomization until disease progression or death from any cause) as assessed by the IRC per IWCLL 2008 criteria.
The primary endpoint of the study is PFS (defined as the time from randomization until disease progression or death from any cause) as assessed by the IRC per IWCLL 2008 criteria.
次要结局
- INV-assessed PFS per IWCLL 2008 criteria.
- INV-assessed ORR (defined as the proportion of patients who achieve a best response of complete remission [CR], complete remission with incomplete bone marrow recovery [CRi], nodular partial remission [nPR], or partial remission [PR]) per IWCLL 2008 criteria.
- IRC-assessed ORR per IWCLL 2008 criteria.
- OS (defined as the time from randomization to the date of death due to any cause)
- PROs as measured by change in scores from baseline to each assessment in the FACIT-Fatigue (will no longer be collected as of Amendment 6.0).
- INV- and IRC-assessed DOR (defined as the time from the first documentation of objective response to the earlier time of disease progression [assessed by the IRC per IWCLL 2008 criteria] or death from any cause)
- TTNT (defined as the time from randomization to institution of nonprotocol-specified treatment for CLL)
研究者
Global Clinical Lead
Scientific
Acerta Pharma B.V.
研究点 (13)
Loading locations...
相似试验
招募中
不适用
Observ Prosp Study of Acalabrutinib in CLL Therapy in Real Clinical Practice in BelarusNCT07288515AstraZeneca50
招募中
不适用
Orelabrutinib Plus Lisaftoclax and Rituximab in Untreated Mantle Cell Lymphoma With High-Risk DiseaseNCT07272499Ruijin Hospital25
尚未招募
2 期
PreVent-ACaLL2024-511072-33-00Rigshospitalet50
进行中（未招募）
3 期
A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects with Rheumatoid Arthritis who are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate (SELECT-COMPARE)2022-501017-31-00Abbvie Deutschland GmbH & Co. KG489
招募中
2 期
Multi-cohort Study to Customize Ibrutinib Treatment Regimens for Patients with Previously Untreated Chronic Lymphocytic Leukemia TAILOR2023-504044-34-00Janssen - Cilag International213