A Phase II Study of Combination Nilotinib and Hyper-CVAD in Patients Newly Diagnosed With Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia Blast-Phase Lymphoid Lineage
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Mayo Clinic
- 试验地点
- 2
- 主要终点
- Disease-free survival rate, defined as a patient who is alive and relapse-free, in patients who achieve a CR during the first 2 courses out to 2 years
研究概览
简要总结
In this study researchers want to find out more about the side effects of a new drug for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML) blastic phase (BP) and if this disease will respond better to nilotinib combined with standard hyper-CVAD therapy rather than hyper-CVAD alone. Hyper-CVAD is a combination of cyclophosphamide, mesna, vincristine (vincristine sulfate), doxorubicin (doxorubicin hydrochloride), dexamethasone, methotrexate, cytarabine, and rituximab (only for patients with cluster of differentiation [CD]20 positive disease). Researchers don't know all the ways that this drug may affect people
详细描述
PRIMARY OBJECTIVES:
I. To determine the clinical efficacy (2-year disease-free survival rate) of nilotinib and combination chemotherapy in adult patients newly diagnosed with Philadelphia chromosome positive B-cell acute lymphoblastic leukemia or blast crisis of chronic myeloid leukemia.
SECONDARY OBJECTIVES:
I. Determine the 2-year overall survival rate. II. Determine the complete response (CR) rates (hematological, cytogenetic, and molecular) in patients treated with this regimen.
III. Determine the CR duration in patients treated with this regimen. IV. Assess the safety and toxicity of this regimen by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Untreated, histological confirmed Philadelphia positive B-cell acute lymphoblastic leukemia or chronic myeloid leukemia blast-phase lymphoid lineage (bilineal, biphenotypic or undifferentiated) per World Health Organization (WHO) criteria; NOTE: Dexamethasone (or corticosteroids) use is allowed if needed before starting chemotherapy; prior imatinib or dasatinib therapy for CML chronic phase (CP) or accelerated phase (AP) is allowed
- •Molecular or cytogenetic documentation of BCR-ABL fusion gene via any of the following: reverse transcriptase-polymerase chain reaction (RT-PCR), G-banding, or fluorescence in situ hybridization (FISH) testing from peripheral blood and/or bone marrow sampling
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Magnesium/potassium/phosphorus within normal limits (WNL)
- •Serum amylase =< 1.5 x upper limit of normal (ULN)
- •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 this situation the direct bilirubin =< 2 x ULN)
- •Alkaline phosphatase =< 3 x ULN
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN
- •Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN
- •Creatinine =< 1.5 x ULN
- •Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- •Provide informed written consent
- •Willing to return to Mayo Clinic Rochester or Mayo Clinic Arizona for follow-up during the active monitoring phase of the study
- •Willing to provide CSF 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 (even if on highly active antiretroviral therapy [HAART])
- •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
- •History of myocardial infarction =< 12 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •Previous treatment with chemotherapy or any other tyrosine kinase inhibitor (prior imatinib or dasatinib for CML-CP/-AP is 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
- •Cardiac ejection fraction (EF) < 45%
- •Clinically significant resting brachycardia (< 50 beats per minute)
- •Corrected QT interval (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
- •Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension)
- •History of or presence of clinically significant ventricular or atrial tachyarrhythmias
- •Patients receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4); use of the following strong or moderate inhibitors are prohibited =< 7 days prior to registration:
- •Strong Inhibitors of CYP3A4; > 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance
- •Indinavir (Crixivan®)
- •Nelfinavir (Viracept®)
- •Atazanavir (Reyataz®)
- •Ritonavir (Norvir®)
- •Clarithromycin (Biaxin®, Biaxin XL®)
- •Itraconazole (Sporanox®)
- •Ketoconazole (Nizoral®)
- •Nefazodone (Serzone®)
- •Saquinavir (Fortovase®, Invirase®)
- •Telithromycin (Ketek®)
- •Moderate Inhibitors of CYP3A4; > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance
- •Aprepitant (Emend®)
- •Erythromycin (Erythrocin®, E.E.S. ®, Ery-Tab®, Eryc®, EryPed®, PCE®)
- •Fluconazole (Diflucan®)
- •Grapefruit juice
- •Verapamil (Calan®, Calan SR®, Covera-HS®, Isoptin SR®, Verelan®, Verelan PM®)
- •Diltiazem (Cardizem®, Cardizem CD®, Cardizem LA®, Cardizem SR®, Cartia XT™, Dilacor XR®, Diltia XT®, Taztia XT™, Tiazac®)
- •Patients receiving any medications or substances that are inducers of CYP3A4; use of the following inducers are prohibited =< 7 days prior to registration
- •* Inducers of CYP3A4
- •Efavirenz (Sustiva®)
- •Nevirapine (Viramune®)
- •Carbamazepine (Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
- •Modafinil (Provigil®)
- •Phenobarbital (Luminal®)
- •Phenytoin (Dilantin®, Phenytek®)
- •Pioglitazone (Actos®)
- •Rifabutin (Mycobutin®)
- •Rifampin (Rifadin®)
- •St. John's wort
- 另有 8 项未显示
研究组 & 干预措施
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: nilotinib (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: rituximab (Biological)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: cyclophosphamide (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: doxorubicin hydrochloride (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: vincristine sulfate (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: methotrexate (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: cytarabine (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: prednisone (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: mesna (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: dexamethasone (Drug)
Treatment (nilotinib, combination chemotherapy)
See Detailed Description
干预措施: leucovorin calcium (Drug)
结局指标
主要结局
Disease-free survival rate, defined as a patient who is alive and relapse-free, in patients who achieve a CR during the first 2 courses out to 2 years
时间窗: 2 years
The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.
次要结局
- Overall survival time, defined as the time from registration to death due to any cause out to 2 years(2 years)
- Complete response (CR) as defined for all evaluable patients who have achieved a CR as the date at which the patient's objective status is first noted to be a CR to the earliest date relapse is documented out to 4 years(Up to 4 years)
- Complete response (CR) rate estimated by the number of patients achieving an objective status of CR during the first 2 courses of treatment divided by the total number of evaluable patients(56 days)
- Maximum grade for each type of adverse event, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0(Up to 30 days after last dose of study drug)