NCT05971251进行中（未招募）1 期
Addition of loNcasTuxImab teSirine to AcalabruTinib in Chronic Lymphocytic Leukemia(Anti-Static Study)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Primary Objective
研究概览
简要总结
Study is a phase I study to determine the maximum tolerated dose of adding Loncastuximab Tesirine to Aclabrutinib in the treatment of chronic lymphocytic leukemia.
详细描述
The study is a phase I study which will employ the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose (MTD).
Approximately 24 Dose-Limiting Toxicity (DLT) evaluable participants will be treated to find MTD with a target DLT rate of 25%, and 4 pre-specified doses. The total number of participants enrolled will depend on the frequency of DLTs and when the MTD is determined. The maximum number of patients at a given dose level is 12.
The dose of acalabrutinib will be fixed and loncastuximab tesirine will be titrated as in dose level table 1 below.
Table 1. Dose levels Dose Level Schedule
- 45 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
- 60 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
- 75 µg/kg Loncastuximab Tesirine + Acalabrutinib 100 mg BID
- 90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent cycles) + Acalabrutinib 100 mg BID
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •- Inclusion Criteria For all patients
- •Diagnosis of CLL according to the IwCLL criteria or SLL according to the World Health Organization (WHO) criteria. This includes previous documentation of:
- •Biopsy-proven small lymphocytic lymphoma OR
- •Diagnosis of CLL according to the IWCLL criteria as evidenced by Peripheral blood lymphocyte count of greater than 5 x109/L .
- •Immunophenotype consistent with CLL defined as the predominant population of lymphocytes share both B cell antigens (CD19, CD20 (typically dim expression), or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc).
- •On therapy with acalabrutinib for a minimum of 3 months without evidence of progression as per IWCLL 2018 criteria.
- •Relapsed or Refractory CLL who have received at least one prior therapy before initiation of acalabrutinib
- •Presence of measurable residual disease in the peripheral blood or bone marrow aspirate by NGS based clonoseq test.
- •Adequate organ function as defined below unless attributed to disease involvement:
- •Liver function (bilirubin ≤ 1.5 × ULN, AST and/or ALT <3 x ULN). Patients with Gilbert Disease are permitted irrespective of bilirubin values.
- •Kidney function (crcl > 30ml/min using Cockroft-Gault, based on actual weight).
- •ANC ≥ 1,000/µL, Hgb > 8, Platelet Count ≥ 50,000/ µL. Use of G-CSF is not permitted for up to 7 days prior to enrollment.
排除标准
- •Exclusion Criteria For all patients
- •Current evidence of central nervous system involvement.
- •Unable to generate clonoseq ID specimen for measurable residual disease tracking.
- •Completion of an autologous hematopoietic stem cell transplantation within 3 months prior to first dose of study drug.
- •Prior allogeneic stem cell transplant within 6 months. The patient should not have any active Graft vs. Host disease (GVH) or should be on immune suppressive agents.
- •Completion of treatment with any radiotherapy, chemotherapy, antibody, immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of the drug, whichever is shorter) prior to the first dose of study drug. Patients may be enrolled after a minimum of 2 weeks of radiation if radiation was for palliative intent.
- •Progression of disease on BTK inhibitor.
- •Unable to tolerate full dose of acalabrutinib at 100 mg twice a day.
- •Inability to swallow and retain oral medications.
- •Pregnant women are excluded from this study.
- •Any active, concurrent, significant illness or disease (other underlying lymphoma) or clinically significant findings including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the patient from participation in the study such as:
- •active infection requiring systemic therapy ≤10 days before the first dose of study drug
- •unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association [NYHA] II, III, IV;), myocardial infarction ≤6 months prior to first study drug, uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study drug
- •Significant (as defined by study doctor) pulmonary disease or disorder
- •any severe or uncontrolled other disease or condition which might increase the risk associated with study participation
- •Vaccination with live, attenuated vaccines within 28 days prior to the first dose of study medication.
- •Receiving systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). The use of inhaled corticosteroids is permitted.
- •Corticosteroids ≥ 10 mg of prednisone within the last 7 days.
- •Has had a solid organ transplant within the last 3 years. Note: Patients who have had a Solid organ transplant >3 years ago are eligible if there are no signs/symptoms of graft versus host disease (GvHD) and off immunosuppressive medications as per above.
- •Known history of hypersensitivity to loncastuximab tesirine
- •Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
- •Breastfeeding or pregnant
- •Any other malignancy known to be active, with the exception of
- •Cervical carcinoma of Stage 1A (1A1,1A2) and 1B (1B1,1B2,1B3)
- •Non-invasive basal cell or squamous cell skin carcinoma
- •Non-invasive, superficial bladder cancer
- •Prostate cancer with a current PSA level < 0.1 ng/mL
- •Any curable or localized cancer with a CR of > 2 years' duration.
研究组 & 干预措施
Dose Level 1:
Experimental
45 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles
干预措施: Loncastuximab Tesirine and Acalabrutinib (Drug)
Dose Level 2
Experimental
60 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles
干预措施: Loncastuximab Tesirine and Acalabrutinib (Drug)
Dose Level 3
Experimental
75 µg/kg Loncastuximab Tesirine every 21 days + Acalabrutinib 100 mg BID for 12 cycles
干预措施: Loncastuximab Tesirine and Acalabrutinib (Drug)
Dose level 4:
Experimental
90 µg /kg Loncastuximab Tesirine (for first 2 cycles followed by 75µg/kg for subsequent 10 cycles) + Acalabrutinib 100 mg BID for a total of 12 cycles.
干预措施: Loncastuximab Tesirine and Acalabrutinib (Drug)
结局指标
主要结局
Primary Objective
时间窗: 12 months
Recommended phase 2 dose of loncastuximab tesirine in combination with acalabrutinib
次要结局
- Secondary Objective 4(12 months)
- Secondary Objective 6(12 months)
- Secondary Objective 1(6 months)
- Secondary Objective 2(12 months)
- Secondary Objective 3(12 months)
- Secondary Objective 5(12 months)
- Secondary Objective 7(12 months)
研究者
Aditi Saha, MD
Assistant Professor, Department of Medicine
University of Alabama at Birmingham
研究点 (1)
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