NCT07755202尚未招募2 期
A Phase 2 Trial of Gilteritinib in Combination With Azacitidine and Venetoclax to Overcome Venetoclax Resistance in Patients With Relapsed/Refractory FLT3-wild Type Acute Myeloid Leukemia
Florian Kuchenbauer1 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2026年9月1日最近更新:
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Efficacy of triplet regimen on AML FLT3-wt participants
研究概览
简要总结
The goal of this clinical trial is to learn if gilteritinib-azacitidine-venetoclax combination drug therapy works to treat adults with FLT3-wt acute myeloid leukemia (AML). It will also learn about the safety and efficacy of this treatment. The main question this clinical trial aims to answer are:
- Will adding gilteritinib to standard-of-care therapy azacitidine-venetoclax show be more effective in treating AML FLT3-wt patients who have previously been treated with azacitidine and/or venetoclax for their disease and have had their cancer come back (relapsed) or have stopped responding to treatment (refractory)?
All participants in this trial will receive the combination therapy. Participants will be on repeated 28-day cycles, for a minimum of 2 cycles, while on the study
Participants will:
- Take the gilteritinib once daily, every day
- Take azacitidine and venetoclax on days 1-7 of each cycle
- Keep a daily dose diary of the days and times they have taken their treatments
- Visit the clinic every 4 weeks for checkups and tests
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
- •Participants must meet all the following inclusion criteria to be eligible for participation in this trial.
- •Age ≥ 18 years old at the time of informed consent.
- •Pathologically confirmed diagnosis of AML previously treated with azacitidine and venetoclax that are azacitidine and venetoclax-refractory, defined as:
- •2a. Primary refractory: Defined as no complete remission (CR) or CR with incomplete recovery (CRi) following at least 2 cycles of azacitidine and venetoclax with AML blasts ≥5% in the bone marrow, or 2b. Relapsed: Defined as recurrence of AML blasts ≥5% in the bone marrow after a previous CR or CRi to azacitidine and venetoclax
- •Confirmed to be negative for FLT3- internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations on repeat clinical testing following their last line of therapy
- •Adequate functional status (ECOG ≤ 2)
- •Participant is willing to provide informed consent and comply with trial procedures
- •Participants of either biological sex must be able and willing to use Health-Canada approved effective contraception methods starting 2-weeks prior to trial treatment, throughout the trial, and for 6 months following the last dose of trial drugs
- •For participants of child-bearing potential (menstruation within <2 years): negative serum pregnancy test within 14-days prior to enrollment.
- •8. Not currently breastfeeding and will not breastfeed while on the trial and for at least 2 months following the last trial dose.
- •Waivers to the inclusion criteria will NOT be allowed.
排除标准
- •Participants are excluded from the trial if any of the following criteria apply:
- •1. Diagnosis of acute promyelocytic leukemia (APL), BCR-ABL positivity, or favorable risk AML
- •Currently considered as eligible for intensive chemotherapy treatment in the opinion of the Investigator
- •Inadequate organ function, defined as: 3a. Liver function: Serum aspartate aminotransferase and alanine aminotransferase ≥ 2.5 x upper limit of normal (ULN) and total bilirubin ≥ 1.5 x ULN 3b. Renal function: estimated glomerular filtration rate of < 30 mL/min as calculated by the Modification of Diet in Renal Disease equation.
- •3c. Cardiac function: New York Heart Association (NYHA) class 3 or 4 heart failure or known history of left ventricular ejection fraction ≤ 40% or known history of prolonged QTc syndrome
- •Corrected QTc of > 450ms that is not corrected on repeat electrocardiogram (ECG) testing
- •Active and untreated CNS leukemia
- •Active solid organ malignancy requiring treatment in the last 24 months, with the exception of: 6a. Treated nonmelanoma skin cancer 6b. Completely treated breast carcinoma that is considered cured 6c. Completely treated cervical carcinoma that is considered cured 6d. Localized breast or prostate cancer receiving androgen deprivation therapy 6e. A previously treated malignancy that is considered cured with minimal risk of recurrence
- •Extramedullary disease without concomitant marrow based disease (blasts ≤5%)
- •Uncontrolled, active infection or untreated hepatitis B, C, or HIV
- •Known allergy or intolerance to azacitidine, venetoclax, or gilteritinib
- •Any comorbidity that the investigator believes would be incompatible with safe receipt or therapy
- •Inability to comply with requirements of the trial protocol
- •Pregnancy or breastfeeding
- •Unable or unwilling to use Health Canada-approved highly effective methods of contraception (i.e., hormonal contraceptives, vasectomy, tubal ligation, or double-barrier method), or abstinence while on the trial and for at least 6 months following the last dose of trial drugs.
- •Waivers to the exclusion criteria will NOT be allowed.
研究组 & 干预措施
All Participants
Experimental
administration of combination therapy gilteritinib-azacitidine-venetoclax on repeated 28-day cycles for a minimum of 2 cycles. Gilteritinib will be taken daily and azacitidine-venetoclax on days 1-7 of each cycle.
干预措施: gilteritinib-azacitidine-venetoclax (Combination Product)
结局指标
主要结局
Efficacy of triplet regimen on AML FLT3-wt participants
时间窗: From enrollment to the end of treatment at week 8
the ORR up to two cycles of triplet therapy. ORR is defined as the proportion of participants who achieve a CR, CRi, or MLFS after completing two cycles of the combination therapy
次要结局
- To assess the safety of triplet regimen based on toxicity findings(from enrollment to one month after end of treatment at 12 weeks)
- Impact of triplet regimen on measurable residual disease (MRD) in participants achieving a response(from enrollment to one month after the end of treatment at 12 weeks)
- Impact of study treatment on event-free survival (EFS)(from enrollment to end of study closeout at 36 months)
- Impact of study treatment on relapse-free survival (RFS)(from enrollment to end of study closeout at 36 months)
- Impact of study treatment on overall survival (OS) in AML FLT3-wt patients(from enrollment to end of study closeout at 36 months)
研究者
Florian Kuchenbauer
Hematologist, Leukemia/BMT Program
British Columbia Cancer Agency
研究点 (1)
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