A Phase 1 Study Combining Venetoclax With a Pediatric-Inspired Regimen for Newly Diagnosed Adults With B Cell Ph-Like Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of venetoclax in combination with a pediatric-inspired chemotherapy regimen known as C10403 in treating patients with newly diagnosed B cell acute lymphoblastic leukemia. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. The C10403 regimen is composed of the chemotherapy drugs cytarabine, cyclophosphamide, daunorubicin, mercaptopurine, pegaspargase, vincristine, and methotrexate, all which work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It also consists of prednisone, which is an anti-inflammatory drug that lowers the body's immune response and is used with other drugs in the treatment of some types of some types of cancer. This study may help researchers learn if adding venetoclax to the pediatric-inspired C10403 regimen can be tolerated and help treat older patients.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability of combining venetoclax with the C10403 regimen backbone during induction and consolidation in newly diagnosed adults with B cell acute lymphoblastic leukemia (ALL).
II. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose/schedule (RP2D) of venetoclax in combination with the C10403 regimen.
SECONDARY OBJECTIVES:
I. To estimate complete response (CR) after induction. II. To estimate composite CR (CR or CR with incomplete hematologic recovery [CRi] or CR with partial hematologic recovery [CRh]) after induction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 54 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent of the participant and/or legally authorized representative
- •Age between 18 and 54 years
- •Eastern Cooperative Oncology Group (ECOG) =< 2
- •Histologically confirmed B-cell ALL according to World Health Organization criteria
- •Note: Lymphoblastic leukemia is included as long as there is bone marrow involvement
- •Newly diagnosed disease with >= 5% blasts in the marrow
- •White blood cell count less than 25 x 10^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea or steroid or a single dose of intrathecal chemotherapy prior to treatment may be required (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
- •Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease or underlying leukemia, =< 3 X ULN) (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
- •Aspartate aminotransferase (AST) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
- •Unless it is related to underlying leukemia
- •Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
- •Unless it is related to underlying leukemia
- •Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
- •Left ventricular ejection fraction (LVEF) >= 50%
- •Note: Echocardiogram to be performed within 42 days prior to day 1 of protocol therapy
- •Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. (performed within 14 days prior to Day 1 of protocol therapy unless otherwise stated)
- •If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Agreement by females and males of childbearing potential* to use an effective method of birth control (non-hormonal) or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only
排除标准
- •Leukemia-based therapy with chemotherapy with the exception of:
- •Cytoreduction with steroid or hydroxyurea or a single dose of intrathecal chemotherapy is allowed before initiating the study
- •Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of protocol therapy
- •Subjects who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the first dose of study drug
- •Live vaccines
- •Philadelphia chromosome positive (Ph+; t(9;22)), MLL-rearrangement, t(12;21), and t(1;19)
- •T cell ALL
- •Class III/IV cardiovascular disability according to the New York Heart Association Classification. Subjects with controlled, asymptomatic atrial fibrillation can enroll
- •Parenchymal central nervous system (CNS) involvement requiring cranial radiation
- •Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of enrollment
- •History of acute cardiovascular ischemic event, i.e., myocardial infarction or unstable angina within 6 months of enrollment
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •Clinically significant uncontrolled illness
- •Uncontrolled active infection
- •Other active malignancy
- •Females only: Pregnant or breastfeeding
- •Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Cyclophosphamide (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Methotrexate (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Vincristine Sulfate (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Cytarabine (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Mercaptopurine (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Pegaspargase (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Venetoclax (Drug)
Treatment (venetoclax, C10403 regimen)
See Detailed Description
干预措施: Prednisone (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 30 days after completion of treatment
Will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome.
Dose limiting toxicity
时间窗: During cycle 1 (4 weeks)
Defined as any toxicities that occur during cycle 1, per CTCAE version 5.0, and are considered at least possibly related to venetoclax or the combination of venetoclax and C10403. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, frequency, probable association with the study treatment and reversibility or outcome.
次要结局
- Composite complete response (CR) (CR/ CR with incomplete hematologic recovery [CRi]/ CR with partial hematologic recovery [CRh]) after induction +/- extended induction for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)(At week 4 or 6)
- Minimal residual disease (MRD) negativity after consolidation for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)(At week 12)
- Complete response (CR) after induction +/- extended induction(At week 4 or 6)
- Composite complete response (CR) (CR/ CR with incomplete hematologic recovery [CRi]/ CR with partial hematologic recovery [CRh]) after induction +/- extended induction(At week 4 or 6)
- Minimal residual disease (MRD) negativity after consolidation(At week 12)
- Complete response (CR) after induction +/- extended induction for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)(At week 4 or 6)
- Complete response (CR) after consolidation for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)(Up to 1 year)
- Minimal residual disease (MRD) negativity after induction +/- extended induction for Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL)(At week 4 or 6)
- Leukemia-free survival(Up to 1 year)
- Overall survival(Up to 1 year)
- Complete response (CR) after consolidation(Up to 1 year)
- Minimal residual disease (MRD) negativity after induction +/- extended induction(At day 28)