NCT03063203终止2 期
An Open Label, Multicenter, Phase II Trial Testing Single Agent Decitabine in TP53 Mutated Relapsed/Refractory Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Overall Survival of Participants With TP53 Mutation
研究概览
简要总结
In this study, the investigators seek to determine whether decitabine therapy can improve outcomes, specifically overall survival this selected subset of acute myeloid leukemia (AML) patients with the poorest prognosis based on refractoriness to induction treatment and high risk genetic mutations.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •TP53 mutant AML. The presence of a TP53 mutation should be determined by Genoptix (or institutional preferred equivalent assay). Detection of a TP53 mutation at the time of initial diagnosis is sufficient for enrollment at the time of relapsed/refractory disease. Detection of a TP53 mutation in either the peripheral blood or bone marrow is adequate for enrollment. Alternatively, patients who have not had TP53 mutation analysis performed, but who have > 20% TP53 positive cells by immunohistochemistry detected on a bone marrow aspirate may also be enrolled,29 provided that mutation analysis is requested at the time of enrollment.
- •Relapsed/refractory AML following 7+3 (or similar cytarabine containing induction chemotherapy for AML) disease detected by one of the following methods:
- •bone marrow blasts > 5%, or
- •Hematologics flow cytometry assay (threshold > 0.5%) (alternative equivalent assay may be substituted), or
- •Persistent cytogenetic abnormality (e.g. del5, del17p, etc), by FISH or conventional karotyping, or
- •Persistent TP53 mutation (at least 5 variant reads with at least 50x coverage) determined by Genoptix (or institutional preferred equivalent assay).
- •Patients with > 10% blasts on a day +14 bone marrow biopsy following 7+3 may either be enrolled or may be treated with a course of standard re-induction (e.g. 5+2 or similar) and then re-evaluated for response. Eligible patients will meet any of the above criteria on a subsequent biopsy.
- •Bone marrow and organ function as defined below:
- •Peripheral white blood cell count < 50,000/mcl (patients may receive hydroxyurea as necessary for cytoreduction),
- •Total bilirubin < 1.5 x upper limit of normal,
- •AST and ALT < 2.5 x upper limit of normal,
- •Serum creatinine < 2.0 x upper limit of normal, and,
- •At least 18 years of age.
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable
- •Performance status ≤ 3
排除标准
- •Prior treatment with either decitabine or azacitidine or an investigational agent
- •Acute promyelocytic leukemia with PML-RARA or t(15;17).
- •History of HIV, Hepatitis B, or Hepatitis C infection.
- •Concurrent illness including, but not limited to, ongoing uncontrolled infection, symptomatic NYHA class 3 or 4 congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- •Radiation therapy within 14 days of enrollment.
- •Chemotherapy administration in the 7 days preceding enrollment with the exception of hydroxyurea, which can be continued until Cycle
- •A washout period for oral tyrosine kinase inhibitors (e.g. Jakafi, etc) is not required, although tyrosine kinase inhibitors therapy must be discontinued prior to enrollment.
- •Malignancies (other than AML) requiring active therapy or diagnosed within the last year, with the exception of non-melanoma skin cancer which can be treated or in situ malignancies (such as cervical, breast, prostate, etc.)
- •Currently receiving any other investigational agents.
- •Known central nervous system (CNS) leukemia or testicular involvement of leukemia
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or other agents used in the study.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative urine pregnancy test within 7 days of study entry.
研究组 & 干预措施
Decitabine
Experimental
- Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle
- Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle.
- Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
干预措施: Decitabine (Drug)
Decitabine
Experimental
- Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle
- Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle.
- Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
干预措施: Bone marrow biopsy/aspirate (Procedure)
Decitabine
Experimental
- Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle
- Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle.
- Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
干预措施: Peripheral blood draw (Procedure)
Decitabine
Experimental
- Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle
- Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle.
- Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
干预措施: Skin biopsy (Procedure)
Decitabine
Experimental
- Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle
- Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle.
- Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
干预措施: Buccal swab (Procedure)
结局指标
主要结局
Overall Survival of Participants With TP53 Mutation
时间窗: 1 year
* Overall survival (OS) is defined as the time from enrollment to death due to any cause. For a patient who is not known to be alive at the end of study follow up, observation of OS is censored on the date the patient was last known to be alive * To be evaluable for this outcome measure the participant would have to have received at least one dose of decitabine
次要结局
- Percentage of Responding TP53 Mutated Patients (CR, CRi)(12 weeks)
- Time to Stem Cell Transplant Among Participants Who Are Suitable Candidates for Transplant and Have an Identified Donor(12 weeks)
- Median Time to Leukemia Relapse (TTLR) in Non-transplant Patients(2 years)
- Event-free Survival (EFS)(2 year)
- Average Number of Hospital Days(During cycles 1 and 2 (60 days))
- Response Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment(Through 12 weeks)
- Survival Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment(2 years)
- Response Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML(Through 12 weeks)
- Survival Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML(2 years)
- Response Compared Between Patients With Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations Versus Patients With Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations(12 weeks)
- Survival Compared Between Patients With Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations Versus Patients With Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations(2 years)
- Median Number of Hospital Stays(During cycles 1 and 2 (60 days))
研究者
研究点 (1)
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