NCT05365035招募中2 期
A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- To establish the overall survival (OS).
研究概览
简要总结
To learn if the combination of cladribine, cytarabine, venetoclax, and azacitidine can help to control higher-risk myelodysplastic syndrome (MDS) with excess blasts and/or higher-risk chronic myelomonocytic leukemia (CMML).
详细描述
Primary Objectives:
- To determine the efficacy, safety and tolerability of the combination of cladribine, cytarabine and venetoclax in higher-risk MDS with excess blasts and higher-risk CMML.
- MDS relapsed cohort (Cohort A, N=20): MDS with Int-2 or High risk IPSS and >5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- CMML relapsed cohort (Cohort B, N=10): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS HMA-naïve cohort (Cohort C, N=20): MDS with Int-2 or High risk by IPSS and >10% blasts OR diagnosis
- CMML HMA-naïve cohort (Cohort D, N=10): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of >5cm below costal margin, platelets <100x109/L, Hgb level <10g/dL, WBC >13x109/L, clonal cytogenetic abnormality (other than monosomy Y).
Secondary Objectives:
- To evaluate responses by 2015 IWG MDS/MPN response criteria in patients with MDS/MPN and by 2023 IWG response criteria in all patients (Appendix).
- To assess overall survival (OS), duration of response, leukemia-free survival (LFS), and relapse-free survival (RFS).
- To evaluate proportion of transplant-candidate patients bridged to allogeneic stem-cell transplant.
- Correlative studies including correlation of response with disease subtype and genomic profile.
- To evaluate changes in clonal composition and VAF of identified mutations with therapy.
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
- •1. Age \>/= 18 years.
- •2. Diagnosis of MDS or CMML by WHO and:
- •* MDS relapsed cohort (Cohort A): MDS with IPSS-R score \>3.5 and \>5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- •* CMML relapsed cohort (Cohort B): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- •* MDS HMA-naïve cohort (Cohort C): MDS with IPSS-R score \>3.5 and \>/= 10% blasts
- •* CMML HMA-naïve cohort (Cohort D): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of \>5cm below costal margin or by sonographic volumetric assessment, platelets \<100x109/L, Hgb level \<10g/dL, WBC \>13x109/L, clonal cytogenetic abnormality (other than monosomy Y) or high risk mutations (ASXL1, RUNX1, SETBP1, BRAF, NRAS, KRAS, PTPN11, NF1, CBL).
- •* MDS/MPN relapsed cohort (Cohort E): MDS/MPN-NOS, MDS/MPN with neutrophilia (atypical CML) or MDS/MPN-RS-T with \>5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- •* MDS/MPN HMA-naïve cohort (Cohort F): MDS/MPN-NOS or MDS/MPN with neutrophilia (atypical CML) with
- •* \>/=10% blasts or
- •* with \>5% blasts at least one of the following high-risk features: splenomegaly \>5cm below costal margin, WBC \>13x109/L, high risk cytogenetic or molecular features (ASXL1, SETBP1, i(17q), TP53) or
- •* who might not be deemed to benefit from HMA therapy due to proliferative or extramedullary disease.
- •3. Eastern Cooperative Oncology Group (ECOG) performance status of \ 30 ml/min no end/stage renal disease (using Cockcroft-Gault)
- •5. Adequate hepatic function with total bilirubin 2x ULN, AST or ALT 2.5 xULN unless deemed to be due to underlying disease involvement.
- •6. Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
- •7. Patient must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
- •8. English and Non-English speaking patients will be allowed
排除标准
- •Uncontrolled infection not adequately responding to appropriate antibiotics
- •New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <50% by echocardiogram or multigated acquisition (MUGA) scan.
- •History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.
- •Female patients who are pregnant or lactating.
- •Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermidical jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
- •Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
- •Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
研究组 & 干预措施
cladribine, cytarabine, venetoclax, and azacitidine
Experimental
Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18
干预措施: Cytarabine (Drug)
cladribine, cytarabine, venetoclax, and azacitidine
Experimental
Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18
干预措施: Cladribine (Drug)
cladribine, cytarabine, venetoclax, and azacitidine
Experimental
Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18
干预措施: Azacitidine (Drug)
cladribine, cytarabine, venetoclax, and azacitidine
Experimental
Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18
干预措施: Venetoclax (Drug)
结局指标
主要结局
To establish the overall survival (OS).
时间窗: through study completion, an average of 1 year
次要结局
未报告次要终点
研究者
研究点 (2)
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