A Phase II Study of Combination Daunorubicin and Cytarabine (Ara-c) and Nilotinib (Tasigna) (DATA) in Patients Newly Diagnosed With Acute Myeloid Leukemia and KIT Overexpression
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 34
- 试验地点
- 2
- 主要终点
- Proportion of Complete Responses (CR or CRi) During Induction Therapy
研究概览
简要总结
This phase II trial studies how well daunorubicin hydrochloride, cytarabine, and nilotinib work in treating patients newly diagnosed with acute myeloid leukemia. Drugs used in chemotherapy, such as daunorubicin hydrochloride 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. Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daunorubicin hydrochloride with cytarabine and nilotinib may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the complete response rates of combination nilotinib, cytarabine, and daunorubicin (daunorubicin hydrochloride) in patients newly diagnosed with acute myeloid leukemia (AML) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (Kit) overexpression.
SECONDARY OBJECTIVES:
I. Determine the 2-year overall survival (OS) and disease-free survival (DFS) rates.
II. Determine the complete response duration in patients treated with this regimen.
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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Untreated, histological confirmed acute myeloid leukemia (AML) based on World Health Organization (WHO) 2008 criteria with Kit expression (cluster of differentiation [CD] 117) of myeloblasts >= 20% by flow cytometry from bone marrow aspirate at diagnosis
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Magnesium within normal limits (WNL)
- •Potassium WNL
- •Phosphorus WNL
- •Serum amylase =< 1.5 x upper limit of normal (ULN)
- •Serum lipase =< 1.5 x ULN
- •Total bilirubin =< 1.5 x ULN (does not apply to patients with isolated hyperbilirubinemia [e.g., Gilbert's disease], in that case direct bilirubin should be =< 2 x ULN)
- •Alkaline phosphatase =< 3 x ULN
- •Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN
- •Creatinine =<1.5 x ULN
- •Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- •Provide informed written consent
- •Willing to return to consenting Mayo Clinic (Mayo Clinic's campus in Rochester, Mayo Clinic's campus in Arizona, or Mayo Clinic's campus in Florida) institution for follow-up during the active monitoring phase of the study
- •Willing to provide bone marrow aspirate and blood samples for correlative research purposes
排除标准
- •Any of the following because this study involves investigational agent(s) whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for 3 months after completion of study treatment
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- •Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix
- •Previous treatment with chemotherapy or any other tyrosine kinase inhibitor for a hematological disorder; Exceptions: patients with prior diagnosis of myelodysplastic syndrome (MDS) and/or treatment with hypomethylating agent (azacytidine or decitabine) are not excluded, prior hydroxyurea allowed
- •Impaired cardiac function including any one of the following:
- •Inability to monitor the QT interval on electrocardiogram (ECG)
- •Congenital long QT syndrome or a known family history of long QT syndrome
- •Clinically significant resting brachycardia (< 50 beats per minute)
- •Corrected QT (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- •Myocardial infarction =< 12 months prior to starting study
- •Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
- •History of or presence of clinically significant ventricular, atrial tachyarrhythmias or ejection fraction cutoff
- •Left ventricle ejection fraction < 45%
- •History of, congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •Patients currently receiving treatment with strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and treatment that cannot be either discontinued or switched to a different medication prior to starting study drug; patients receiving any medications or substances that are strong or moderate inhibitors of CYP3A4
- •Use of the following strong or moderate inhibitors is prohibited < 7 days prior to registration
- •Strong inhibitors of CYP3A4/5 > 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance
- •Boceprevir (Victrelis)
- •Clarithromycin (Biaxin, Biaxin XL)
- •Conivaptan (Vaprisol)
- •Grapefruit juice
- •Indinavir (Crixivan)
- •Itraconazole (Sporanox)
- •Ketoconazole (Nizoral)
- •Lopinavir/ritonavir (Kaletra)
- •Mibefradil
- •Nefazodone (Serzone)
- •Nelfinavir (Viracept)
- •Posaconazole (Noxafil)
- •Ritonavir (Novir, Kaletra)
- •Saquinivir (Fortovase, Invirase)
- •Telaprevir (Incivek)
- •Telithromycin (Ketek)
- •Voriconazole (Vfend)
- •Moderate inhibitors of CYP3A4/5 > 2-fold in the plasma AUC values or 50-80% decrease in clearance
- •Amprenavir (Agenerase)
- •Aprepitant (Emend)
- •Atazanavir (Reyataz)
- •Ciprofloxacin (Cipro)
- •Darunavir (Prezista)
- •Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Taztia XT, Tiazac)
- •Erythromycin (Erythrocin, E.E.S. , Ery-Tab, Eryc, EryPed, PCE)
- •Fluconazole (Diflucan)
- •Fosamprenavir (Lexiva)
- 另有 28 项未显示
研究组 & 干预措施
Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride IV over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib PO BID on days 4-14. Patients achieving CR or CRi proceed to consolidation therapy. Patients not achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery receive another course of induction therapy.
CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every 84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cytarabine (Drug)
Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride IV over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib PO BID on days 4-14. Patients achieving CR or CRi proceed to consolidation therapy. Patients not achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery receive another course of induction therapy.
CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every 84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Daunorubicin Hydrochloride (Drug)
Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride IV over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib PO BID on days 4-14. Patients achieving CR or CRi proceed to consolidation therapy. Patients not achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery receive another course of induction therapy.
CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every 84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride IV over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib PO BID on days 4-14. Patients achieving CR or CRi proceed to consolidation therapy. Patients not achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery receive another course of induction therapy.
CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every 84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Nilotinib (Drug)
Treatment (nilotinib, daunorubicin hydrochloride, cytarabine)
INDUCTION THERAPY: Patients receive daunorubicin hydrochloride IV over 10 minutes on days 1-3, cytarabine IV continuously on days 1-7, and nilotinib PO BID on days 4-14. Patients achieving CR or CRi proceed to consolidation therapy. Patients not achieving a significant decrease in bone marrow recovery or CR/CRi upon bone marrow recovery receive another course of induction therapy.
CONSOLIDATION THERAPY: Patients receive cytarabine IV every 12 hours on days 1, 3, and 5, and nilotinib PO BID on days 4-14. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRi proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive nilotinib PO BID on days 1-84. Treatment repeats every 84 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Proportion of Complete Responses (CR or CRi) During Induction Therapy
时间窗: Up to 56 days
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
次要结局
- Duration of Complete Response(2 years)
- Disease Free Survival(DFS) Rate(35 months)
- Incidence of Adverse Events as Assessed by NCI CTCAE Version 4.0(35 months)
- Overall Survival(OS) Rate(39 Months)