2022-502665-15-00招募中2 期
Phase II study of (early) combination salvage therapy with Venetoclax and intensified Decitabine in Relapsed/Refractory AML
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Hematologic remission (defined as morphologically leukemia-free state (MLFS), complete remission (CR), complete remission with incomplete hematological recovery (CRi) or complete remission with partial hematological recovery (CRh)) as best response in bone marrow aspiration cytomorphology*) after one or two cycles of Decitabine/Venetoclax.
研究概览
简要总结
Hematologic remission (best response in bone marrow aspiration cytomorphology, hematologic remission defined as <5% residual bone marrow blasts) after one or two cycles of Decitabine/Venetoclax
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Follow-up
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of AML according to WHO criteria regardless of subtype. Including de novo and transformed MPN and transformed MDS
- •All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
- •All subjects must agree not to share medication
- •2.A. Refractory to induction chemotherapy consisting of Daunorubicin+Cytarabin (“3+7”) based chemotherapy, including CPX351, including combinations with Gemtuzumab-Ozogamicin or with the FLT3-inhibitors Midostaurin or Quizartinib. This trial defines refractory disease as one of the following: i. ≥20% bone marrow blasts** at day 15*** first cycle of intensive induction chemotherapy ii. ≥5-20% bone marrow blasts** at day 15*** of first cycle of intensive induction chemotherapy in patients, in whom relative blast count reduction as compared to initial diagnosis is ≤50% iii. c) ≥5% bone marrow blasts** at day 28**** of first cycle of induction chemotherapy, or at any point during a second cycle of induction chemotherapy OR
- •B. Relapse of AML/MDS IB2 after chemotherapy (≥5% medullary blasts in bone marrow assessment**)
- •Relapse of AML/MDS EB2 after chemotherapy (≥5% medullary blasts in bone marrow assessment)
- •Must be ≥ 18 years at the time of signing the informed consent
- •Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
- •Able to adhere to the study visit schedule and other protocol requirements
- •Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist
- •No known history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) >40% (adjusted for hemoglobin, if available) and FEV1/FVC >50%
- •Subject (male or female (FCBP))1 is willing to use highly effective birth control methods during treatment and for 3 months (male) and 6 months (female) after the end of treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system bilateral tubal occlusion, vasectomized partner2 sexual abstinence3). Female subjects who use hormonal contraceptives should also use a barrier method.
排除标准
- •APL (AML with t(15;17))
- •Not consenting to chemotherapy in general
- •Previous Treatment with allogeneic stem cell transplantation
- •Significant active cardiac disease within 6 months prior to the start of study treatment, including:• New York Heart Association (NYHA) class III or IV congestive heart failure;• Myocardial infarction;• Unstable angina and/or stroke;• Severe cardiac arrhythmias• Left ventricular ejection fraction (LVEF) <40% by ultrasound obtained within 28 days prior to the start of study treatment.
- •Severe obstructive or restrictive ventilation disorder
- •Relapsed FLT3-ITD- or FLT3-TKD-mutated patients, who previously responded (CR, CRi, CRh or MLFS) to a regimen containing a FLT3-inhibitor
- •Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.(Note: Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening)
- •Active infection, including hepatitis B or hepatitis C antibody or Human Immunodeficiency Virus (HIV) infection, that is uncontrolled prior to first dose of study treatment and may interfere with the study objectives or which could expose the patient to undue risk through the participation in the clinical trial; an infection controlled with an approved antibiotic/ antiviral/ antifungal treatment that is not a strong or moderate CYP3A inducer is allowed
- •Immediate life‐threatening, severe complications of leukemia such as uncontrolled bleeding and/or disseminatwed intravascular coagulation
- •Medical History of hypersensitivity to to the active substances of Venetoclax and Decitabin or to any of the excipients listed in the respective SmPCs
- •Women during pregnancy and lactation.
- •Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.
- •Patients with a currently active second malignancy. Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at <30% risk of relapse within one year. However, patients with the following history/concurrent conditions are allowed:• Basal or squamous cell carcinoma of the skin;• Carcinoma in situ of the cervix;• Carcinoma in situ of the breast;• Incidental histologic finding of prostate cancer.
- •Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: patients, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy).
结局指标
主要结局
Hematologic remission (defined as morphologically leukemia-free state (MLFS), complete remission (CR), complete remission with incomplete hematological recovery (CRi) or complete remission with partial hematological recovery (CRh)) as best response in bone marrow aspiration cytomorphology*) after one or two cycles of Decitabine/Venetoclax.
Hematologic remission (defined as morphologically leukemia-free state (MLFS), complete remission (CR), complete remission with incomplete hematological recovery (CRi) or complete remission with partial hematological recovery (CRh)) as best response in bone marrow aspiration cytomorphology*) after one or two cycles of Decitabine/Venetoclax.
次要结局
- Safety and feasibility of combining Venetoclax with a timedense immediate application of the hypomethylating agent Decitabine evaluated by the incidence of CTCAEs ≥ grade 3 until day 30 after therapy application and times to hematopoietic recovery (absolute neutrophil counts ≥0.5 and ≥1.0 x 109/L; platelets ≥50 and ≥100 x 109/L) after each chemotherapy treatment cycle, defined as the time from the start of the cycle until recovery
- MRD assessment (MRD including qPCR for established MRD markers and NGS for exploratory MRD markers) at each remission assessment
- Infectious complications CTCAEs >=grade 3
- Time-to-transplant from diagnosis of primary induction failure to infusion of allogeneic stem cells
- ECOG prior to start of potential conditioning for transplant
- PFS and OS at Follow-up Visit (100 days after EOT) and time dependent
- Mortality at 30 days post start of salvage therapy
- Quality of life assessment at screening (additional at the end of each cycle Venetoclax/Decitabine) and at the end of the trial (follow up)
- Hospitalisation days, defined as days in hospital from day 1 of therapy until day 30 after EOT
研究者
Claudia Lengerke
Scientific
Universitaetsklinikum Tuebingen
研究点 (1)
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