Phase II Trial of Vosaroxin in Combination With Infusional Cytarabine in Patients With Untreated AML
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Complete Remission Rate (CR)
研究概览
简要总结
This phase II trial studies how well vosaroxin and cytarabine work in treating patients with untreated acute myeloid leukemia. Drugs used in chemotherapy, such as vosaroxin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
详细描述
PRIMARY OBJECTIVES:
I. To assess the rate of complete remission (CR) after induction therapy with the combination of "7+V" (vosaroxin and standard dose infusional cytosine arabinoside [ara-C]) for patients with newly diagnosed, previously untreated acute myelogenous leukemia (AML).
SECONDARY OBJECTIVES:
I. Frequency of grade 3-5 adverse events related to administration of "7+V".
II. To evaluate for the presence of minimal residual disease (MRD) remaining after "7+V" induction and/or re-induction.
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
- •Ability to provide informed consent
- •Ability to tolerate intensive therapy with vosaroxin 90 mg/m^2 and cytarabine
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 at time of study entry
- •Morphologically confirmed new diagnosis of AML in accordance with World Health Organization (WHO) diagnostic criteria
- •Patients who have received hydroxyurea alone or have previously received "non-cytotoxic" therapies for myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) (e.g., thalidomide or lenalidomide, 5-azacytidine or decitabine, histone deacetylase inhibitors, low-dose Cytoxan, tyrosine kinase or dual tyrosine kinase [TK]/SRC proto-oncogene, non-receptor tyrosine kinase [src] inhibitors) will be allowed
- •Serum creatinine =< 2.0 mg/dL
- •Hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) =< 2.5 x upper limit of normal
- •Total bilirubin =< 1.5 x upper limit of normal unless clearly related to Gilbert's disease, hemolysis or leukemic infiltrate
- •FOR PATIENTS IN STAGE 1 (PATIENTS #1-#17)
- •>= 55 years of age with AML of any risk classification, or 18-54 years of age with high-risk AML disease based on one of the following:
- •Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD)
- •Treatment-related myeloid neoplasms (t-AML/t-MDS)
- •AML with FMS-like tyrosine kinase 3 (FLT3) - internal tandem duplication (ITD)
- •Myeloid sarcoma
- •AML with multilineage dysplasia (AML-MLD)
- •Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13; trisomy 21; complex karyotypes (>= 3 clonal abnormalities); monosomal karyotypes
- •FOR PATIENTS IN STAGE 2 (ENROLLED PATIENT #18 AND BEYOND)
- •>= 55 years of age with AML of any risk classification, or 18-54 years of age with intermediate or high risk AML as defined by National Comprehensive Cancer Network (NCCN) risk assignment
排除标准
- •STAGES 1 AND 2
- •Patients with acute promyelocytic leukemia (APL) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or fluorescence in situ hybridization (FISH) or molecular testing
- •Any previous treatment with vosaroxin
- •Concomitant chemotherapy, radiation therapy
- •For patients with hyperleukocytosis with > 50,000 blasts/μL; leukapheresis or hydroxyurea may be used prior to study drug administration for cytoreduction at the discretion of the treating physician
- •Active, uncontrolled infection
- •Patients with infection under active treatment and controlled with antibiotics, antivirals, or antifungals are eligible
- •Chronic hepatitis is acceptable
- •Active, uncontrolled graft vs. host disease (GVHD) following allogeneic transplant for non-AML condition (e.g. MDS, lymphoid malignancy, aplastic anemia); patients with GVHD controlled on stable doses of immunosuppressants are eligible
- •Presence of other life-threatening illness
- •Left ventricular ejection fraction (LVEF) < 40% as measured by echocardiogram or multi gated acquisition scan (MUGA)
- •Known or suspected central nervous system (CNS) involvement of active AML
- •Other active malignancies including other hematologic malignancies or other malignancies within 12 months before randomization, except nonmelanoma skin cancer or cervical intraepithelial neoplasia
- •History of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (CVA/TIA) within 3 months before randomization
- •Prior or current therapy:
- •Hydroxyurea or medications to reduce blast count within 24 hours before randomization
- •Treatment with an investigational product within 14 days before randomization, or not recovered from all acute effects of previously administered investigational products
- •Renal insufficiency requiring hemodialysis or peritoneal dialysis
- •Pregnant or breastfeeding
- •Known human immunodeficiency virus (HIV) seropositivity
- •Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
- •ADDITIONAL EXCLUSION CRITERIA APPLIED TO STAGE 1
- •Patients 18-54 years of age with "good risk" AML defined as the presence of t(8;21), inv(16), or t(16;16) as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or FISH
- •Patients with t(8;21), inv(16), t(16;16) who are unable to receive anthracycline based induction will be allowed to enroll provided the medical reason they are unable to receive anthracyclines is clearly documented and provided they fulfill all other eligibility and criteria
研究组 & 干预措施
Treatment (vosaroxin, cytarabine)
Patients receive vosaroxin IV on days 1 and 4 and cytarabine IV continuously on days 1-7 (Induction I). Patients with residual leukemia and for whom a second course is indicated in the judgment of the investigator may undergo a second course of treatment (Induction II) 14-57 days after day 1 of Induction I.
干预措施: Cytarabine (Drug)
Treatment (vosaroxin, cytarabine)
Patients receive vosaroxin IV on days 1 and 4 and cytarabine IV continuously on days 1-7 (Induction I). Patients with residual leukemia and for whom a second course is indicated in the judgment of the investigator may undergo a second course of treatment (Induction II) 14-57 days after day 1 of Induction I.
干预措施: Vosaroxin (Drug)
结局指标
主要结局
Complete Remission Rate (CR)
时间窗: Up to 3 months
CR is calculated as the percentage of patients with complete remission after the therapy. The response criteria is based on International Working Group Criteria. Complete Remission: Neutrophils(cells/μl)\>1000, Platelets (plt/μl)≥ 100,000,Bone marrow blasts (%) \<5; CR with incomplete count recovery (CRi): meets criteria for CR except for neutrophils ≤1000 or Meets criteria for CR except for platelets\< 100,000; Partial Remission: CR except for Bone marrow blasts (%) Decrease of ≥ 50% to value between 5% and 25%; Treatment Failure:Persistent acute myeloid leukemia in blood or bone marrow, or therapy fails to achieve a remission of any category, or death prior to response assessment
次要结局
- Leukemia-free Survival (LFS or DFS)(The time from complete remission to disease progression or death for any reason, assessed up to 1 year)
- Event-free Survival(From start of therapy up to 1 year)
- Frequency of Grade 3-5 Adverse Event Related to Cytarabine and Vosaroxin (7+V)(Up to 3 months)
- Minimal Residual Disease(Up to 3 months)
- Overall Survival(The time from start of therapy to death, assessed up to 1 year)
- Rate of CR/CRi(Up to 3 months)
研究者
Sanjay Mohan
Assistant Professor of Medicine, Division of Hematology/Oncology
Vanderbilt-Ingram Cancer Center