Phase II Study of Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed By Consolidation With Cladribine Plus LDAC Alternating With Decitabine in Patients With Untreated Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Disease-Free Survival (DFS)
研究概览
简要总结
The goal of this clinical research study is to learn if cladribine given in combination with low-dose cytarabine (LDAC) and decitabine can help control the disease in patients with AML or MDS. The safety of this drug combination will also be studied.
Cladribine is designed to interfere with the cell's ability to process DNA (the genetic material of cells). It can also insert itself into the DNA of cancer cells to stop them from growing and repairing themselves.
Cytarabine is designed to insert itself into DNA of cancer cells to stop them from growing and repairing themselves.
Decitabine is designed to damage the DNA of cells, which may cause cancer cells to die.
This is an investigational study. Cladribine is FDA approved and commercially available for use in patients with hairy cell leukemia. Its use in patients with AML is investigational.
Cytarabine is FDA approved and commercially available for use in patients with AML.
Decitabine is FDA approved and commercially available for use in patients with MDS. Its use for patients with AML is investigational.
Up to 160 patients will take part in this study. All will be enrolled at MD Anderson.
详细描述
Study Drug Administration:
If you are eligible to take part in this study, you will receive 1 or 2 cycles of induction therapy followed by up to 17 cycles of consolidation therapy. Each study cycle is 4 weeks.
Induction Cycles:
On Days 1-5, you will receive cladribine by vein over 1-2 hours.
On Days 1-10, you will give yourself the cytarabine by injection twice a day about 12 hours apart. You will receive instructions on how give yourself the injections.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •Patients with previously untreated AML or high risk MDS (>/= 10 % blasts or IPSS >/= intermediate-2). Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2g is allowed. Patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML.
- •Age >/= 60 years. Patients aged < 60 years who are unsuitable for standard induction therapy may be eligible after discussion with PI
- •Adequate organ function as defined below:
- •liver function (bilirubin < 2mg/dL, AST and/or ALT <3 x ULN)
- •kidney function (creatinine < 1.5 x ULN ).
- •ECOG performance status of ≤
- •A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- •Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.
- •Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine.
排除标准
- •Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patient with documented hypersensitivity to any of the components of the chemotherapy program.
- •Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
- •Inclusion Criteria:
- •8. Patients with previously untreated AML who are not currently eligible for other frontline clinical trials of AML therapy. Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2g is allowed. Patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML.
- •9. Age >/= 18 years who are unsuitable for standard induction therapy are eligible after discussion with PI
- •Patients must have one of the following:
- •Creatinine >/= 2 mg/dL
- •Total bilirubin >/= 2 mg/dL
- •ECOG Performance Status equal to 3 or 4
- •Is ineligible for participation in a protocol of higher priority
- •A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- •12. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.
- •13. Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine.
- •Exclusion Criteria:
- •5. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
- •6. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, unless these illnesses are judged to be related to the underlying leukemia.
- •7. Patient with documented hypersensitivity to any of the components of the chemotherapy program.
- •8. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
- •Inclusion Criteria:
- •Patients with relapsed and or refractory AML who have received at least one prior therapy for their AML.
- •Age >/= 18 years.
- •Adequate organ function as defined below:
- •liver function (bilirubin < 2mg/dL, AST and/or ALT <3 x ULN)
- •kidney function (creatinine < 1.5 x ULN ).
- •ECOG performance status of ≤
- •A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
- •Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.
- •Prior therapy with venetoclax will be allowed.
- •Exclusion Criteria
- •Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patient with documented hypersensitivity to any of the components of the chemotherapy program.
- •Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation
研究组 & 干预措施
Cladribine + Cytarabine Alt. with Decitabine
Induction cycle: Cladribine intravenous (IV) over approximately 1 to 2 hours, daily on days 1-5 combined with Cytarabine subcutaneous (SQ) twice daily on days 1-10. Cytarabine should be administered approximately 3-6 hours following the start of the cladribine infusion.
Consolidation cycle: Cladribine IV over 1 to 2 hours, daily on days 1-3 combined with Cytarabine SQ twice daily on days 1-10. Cytarabine should be administered 3-6 hours following the start of the cladribine infusion.
Alternating with: Decitabine IV over 1 to 2 hours, daily on days 1-5.
干预措施: Cytarabine (Drug)
Cladribine + Cytarabine Alt. with Decitabine
Induction cycle: Cladribine intravenous (IV) over approximately 1 to 2 hours, daily on days 1-5 combined with Cytarabine subcutaneous (SQ) twice daily on days 1-10. Cytarabine should be administered approximately 3-6 hours following the start of the cladribine infusion.
Consolidation cycle: Cladribine IV over 1 to 2 hours, daily on days 1-3 combined with Cytarabine SQ twice daily on days 1-10. Cytarabine should be administered 3-6 hours following the start of the cladribine infusion.
Alternating with: Decitabine IV over 1 to 2 hours, daily on days 1-5.
干预措施: Cladribine (Drug)
Cladribine + Cytarabine Alt. with Decitabine
Induction cycle: Cladribine intravenous (IV) over approximately 1 to 2 hours, daily on days 1-5 combined with Cytarabine subcutaneous (SQ) twice daily on days 1-10. Cytarabine should be administered approximately 3-6 hours following the start of the cladribine infusion.
Consolidation cycle: Cladribine IV over 1 to 2 hours, daily on days 1-3 combined with Cytarabine SQ twice daily on days 1-10. Cytarabine should be administered 3-6 hours following the start of the cladribine infusion.
Alternating with: Decitabine IV over 1 to 2 hours, daily on days 1-5.
干预措施: Decitabine (Drug)
结局指标
主要结局
Disease-Free Survival (DFS)
时间窗: Day 21
Disease-free survival (DFS) defined as the time interval from treatment start until clinically significant disease progression or death, whichever occurred first. Participants followed for survival every 6 to 12 months after completion of active treatment. Study continuously monitored for primary endpoint, DFS using the method of Thall, Wooten, and Tannir.
次要结局
未报告次要终点