EUCTR2016-003353-16-DE进行中（未招募）1 期
A Phase 1b/2 Study of Entospletinib (GS-9973) Monotherapy and in Combination with Chemotherapy in Patients with Acute Myeloid Leukemia (AML)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 148
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •- Subjects age = 18 with previously untreated AML by WHO criteria, excluding acute promyelocytic leukemia (M3), who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician
- •- Subjects age > 70 years with previously untreated AML by WHO criteria, excluding acute promyelocytic leukemia (M3)
- •- Subjects age = 70 years with previously untreated AML by WHO criteria, excluding acute promyelocytic leukemia (M3), who refuse or are unable to receive 7+3 as determined by the treating physician
- •Groupe C Phase 1b
- •- Subjects age = 18 years with relapsed/refractory AML by WHO criteria, excluding acute promyelocytic leukemia (M3)
- •- Subjects with previously untreated AML by WHO criteria, excluding acute promyelocytic leukemia (M3), and who would have met disease eligibility criteria for Group A or B but refuse or are unable to receive 7+3 or decitabine chemotherapy as determined by the treating physician
- •Group C Phase 2 (Dose Expansion)
- •- Cohort C1A: Subjects age = 18 years with relapsed/refractory AML by WHO criteria, excluding acute promyelocytic leukemia (M3)
- •- Cohort C2: Subjects age = 18 years with relapsed/refractory AML with MLL
- •- Cohort C3: Subjects with previously untreated AML by WHO criteria, excluding acute promyelocytic leukemia (M3), and who would have met disease eligibility criteria for Group A or B but refuse or are unable to receive chemotherapy and hypomethylating agent as determined by the treating physician
- •ALL patients must meet all of the following inclusion criteria to be eligible for participation in this study:
- •1) Male or female = 18 years of age with a diagnosis AML (M0-M7, except M3).
- •2) All acute toxic effects of any prior anti-leukemia therapy resolved to Grade = 1 before the start of study treatment (with the exception of alopecia [any grade permitted], or bone marrow parameters [any grade permitted] due to leukemia in the investigators opinion).
- •3) ECOG performance status less than or equal to 2.
- •4) Life expectancy of at least 3 months.
- •5) Meet required screening laboratory criteria unless leukemia related.
- •6) Left Ventricular Ejection Fraction (LVEF) = 45% confirmed by ECHO and no clinical evidence of congestive heart failure.
- •7) For female subjects of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 30 days following the last dose of ENTO or as recommended in the prescribing information for other co-administered study drugs (whichever is later).
- •For male subjects of childbearing potential having intercourse with females of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol recommended method of contraception from the start of study treatment throughout the study treatment period and for 90 days following the last dose of ENTO or as recommended in the prescribing information for other co-administered study drugs (whichever is later), and to refrain from sperm donation from the start of study treatment throughout the study treatment period and for 90 days following the last dose of ENTO or as recommended in the prescribing information for other co-administered study drugs (whichever is later).
- •Note: See Appendix 4 for definition of childbearing potential and information regarding recommendations for contraceptio
排除标准
- •1) Patients with acute promyelocytic leukemia (M3)
- •2) Known active central nervous system or leptomeningeal leukemic involvement. Note: Central nervous system testing (CSF analysis) is only required in patients with suspected involvement based on symptoms or signs.
- •3) Treatment with proton pump inhibitors (PPIs) within 7 days prior to enrollment. Note: PPIs are likely to interfere with ENTO absorption, thus requiring a 7-day washout period. H2 blockers and antacids will be allowed for use during the protocol
- •4) History of active non-myeloid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for > 1 year prior to start of study therapy, or any other cancer that has been in complete remission without treatment for = 5 years prior to enrolment. Subjects who are on prophylaxis with long-term adjuvant hormonal therapy and are = 5 years from therapy for their primary tumor are eligible for enrollment.
- •5) Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection at the time of start of study treatment. Note: Patients with localized fungal infections of skin or nails are eligible.
- •6) Ongoing, drug-induced liver injury, known chronic active hepatitis C Virus (HCV), chronic active hepatitis B Virus (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
- •7) Ongoing (within the past 6 weeks) hepatic encephalopathy.
- •8) Ongoing drug-induced pneumonitis.
- •9) Ongoing inflammatory bowel disease.
- •10) Ongoing alcohol or drug addiction as determined by investigator.
- •11) Pregnancy or breastfeeding.
- •12) History of prior allogeneic bone marrow progenitor cell or solid organ transplantation. Note: prior allogeneic bone marrow progenitor cell or solid organ transplantation is NOT an exclusion criteria for Cohort C2 ie, MLL cohort.
- •13) Ongoing immunosuppressive therapy, including systemic chemotherapy for treatment of leukemia. Patients may not have received AML-directed therapy prior to enrollment other than Hydrea or apheresis, if de-novo or for current relapse, except for patients defined as refractory disease at study enrollment. Concurrent use of methotrexate for rheumatologic conditions is permitted.
- •Note: Patients may use topical, enteric, or inhaled corticosteroids as therapy for comorbid conditions and systemic steroids for autoimmune anemia and/or thrombocytopenia. Ongoing use of low dose systemic corticosteroids (<5 mg/day of methylprednisolone or equivalent) for rheumatologic conditions is permitted. During study participation, patients may receive systemic or other corticosteroids needed for treatment-emergent comorbid conditions.
- •14) Concurrent participation in an investigational drug trial with therapeutic intent defined as prior study therapy within 14 days prior to study treatment.
- •15) Any other prior or ongoing condition that, in the opinion of the investigator, could adversely affect the safety of the patient or impair the assessment of study results .
- •16) Inability to tolerate oral medications, symptomatic disease significantly affecting gastrointestinal function manifested
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