Phase Ib/II Study of IDH2 Inhibitor Enasidenib in Combination With BCL2 Inhibitor Venetoclax in Patients With IDH2-Mutated Myeloid Malignancies (ENAVEN-AML)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
The purpose of this research study is to see how safe and tolerable, and to find the highest or best dose, of an investigational combination of drugs called enasidenib and venetoclax, in patients with relapsed (the cancer has come back) or refractory (the cancer does not respond or have stopped responding to treatment) acute myeloid leukemia (AML, a type of blood cancer). This study will also see how useful the combination of enasidenib and venetoclax is in the treatment of patients with relapsed or refractory AML.
详细描述
This study will have two parts: Phase 1b and Phase 2. The part that patients may participate in will depend on when they join the study.
In the phase 1b portion of the study, small groups participants will receive increasing doses of venetoclax in combination with a flat dose of enadisenib until the highest dose or best dose of venetoclax that is safe and tolerable in combination with enadisenib is found.
In the phase 2 portion of the study, an additional group of participants will receive the highest or best dose of venetoclax found in the Phase 1b portion of the study with a flat dose of enadisenib to see how useful the combination is in treating relapsed or refractory acute myeloid leukemia (AML).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance score of ≤2
- •IDH2 (R140 or IDH R172) mutated AML disease status as determined by local laboratory
- •Relapsed and/or refractory acute myeloid leukemia (AML). Treatment-naïve patients who are not eligible for standard induction chemotherapy or high-risk myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) may also be eligible.
- •Adequate hepatic function
- •Adequate renal function
- •Willing and able to provide informed consent
- •In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic and non-cytotoxic (immunotherapy) agents
排除标准
- •Known allergy or hypersensitivity to enasidenib or venetoclax
- •Previously received either an IDH2 inhibitor or BCL2 inhibitor
- •With any uncontrolled clinically significant medical conditions
- •The use of other chemotherapeutic agents or anti-leukemic agents, radiotherapy or other investigational therapy is not permitted during study with exceptions
- •Receiving concomitant treatment with strong cytochrome P450 2A (CYP3A4) inhibitors within 3 days of start of study therapy
- •Receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, St. John's Wort) within 3 days of start of study therapy.
- •Taking the following sensitive CYP substrate medications that have a narrow therapeutic range are excluded from the study unless the subject can be transferred to other medications at least 5 half-lives prior to the start of study treatment: paclitaxel and docetaxel (CYP2C8), phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline, and tizanidine (CYP1A2)
- •Active graft-versus-host-disease (GVHD) status post stem cell transplant
- •Severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications
- •Concurrent active malignancy under treatment
- •Administration or consumption of any of the following within 3 days prior to first dose of study drug: grapefruit or grapefruits products, Seville oranges (including marmalade containing Seville oranges) and start fruit
- •Heart-rate corrected QT (QTc) interval ≥480 msec (Fridericia's formula) except for underlying right-bundle branch block (RBBB).
- •Positive for HIV
- •Subject has an unacceptable white blood cell count
- •Positive urine pregnancy test,
- •Participants who not willing to maintain adequate contraception
研究组 & 干预措施
Venetoclax and Enadisenib
Enasidenib and venetoclax will be taken by mouth (orally), once a day, every day, continuously.
Every 28-day period will be called a cycle. Participants will start venetoclax alone on Cycle 1 Day 1 and continue the study drug alone until Day 15. On Day 15, participants will take enasidenib and venetoclax together and will continue to take the combination of study drugs until intolerable side effects or disease worsening.
干预措施: Enasidenib (Drug)
Venetoclax and Enadisenib
Enasidenib and venetoclax will be taken by mouth (orally), once a day, every day, continuously.
Every 28-day period will be called a cycle. Participants will start venetoclax alone on Cycle 1 Day 1 and continue the study drug alone until Day 15. On Day 15, participants will take enasidenib and venetoclax together and will continue to take the combination of study drugs until intolerable side effects or disease worsening.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 3 years
Dose Limiting Toxicity
时间窗: 28 days
Maximum tolerated dose or Recommended Phase 2 Dose
时间窗: 3 years
Dose indicated by the mTPI decision
Duration of Response
时间窗: 3 years
The time from the date of first response until progression, relapse, death, or last follow-up.
次要结局
- Event Free Survival(3 years)
- Overall Survival(3 years)