Induction Therapy With Pacritinib Combined With Decitabine or Cytarabine in Older Patients With Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Complete Remission Rate
研究概览
简要总结
The purpose of this study is to see if a medicine called pacritinib is both safe and effective as a study intervention for patients with AML in combination with either decitabine or cytarabine. Pacritinib is an experimental drug that is being studied to treat acute myeloid leukemia (AML). Decitabine and cytarabine are both FDA approved drugs that are used in treatment of AML. Pacritinib is being tested in clinical trials and has not been submitted to the U.S. Food and Drug Administration (FDA) for approval for any indications. Pacritinib is a drug that is designed to slow down the growth of leukemic cells.
详细描述
This is a single-center, open label, two-arm phase II study of clinical activity of pacritinib in older patients newly diagnosed with AML combined with either decitabine or cytarabine. In this study, approximately 61 patients will be enrolled at the Weill Cornell Medical College. Arm A consists of pacritinib and decitabine and will enroll 31 subjects, and Arm B consists of pacritinib and cytarabine and will enroll 30 subjects. Arm A and B will enroll sequentially. The dose of pacritinib will be 200mg twice a day continuously.
Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.
Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
Treatment may be given on an outpatient basis if hospitalization is not otherwise required. Every effort should be made to give decitabine or cytarabine consecutively for 10 days; however if interruption is needed, discussion will be held with the medical monitor and the investigator.
The first day of a cycle will be defined as the day on which decitabine or cytarabine is started. First treatment will take place on Cycle 1, day 1. Hydroxyurea may be used at the investigator's discretion for the first 28 days on Cycle 1 to maintain white blood cell count (WBC) <30,000/µl. Bone marrow biopsy and aspiration will be performed between days 22-56 of each cycle and the subsequent treatment cycle will be started between days 22-56, at the investigator's discretion. Ideally, cycles will be administered at 28-day intervals, but treatment delays of decitabine or cytarabine up to 56 days will be permitted to allow resolution of non-hematologic and non-disease-related hematologic toxicities. Granulocyte-stimulating cytokine support will be permitted at the investigator's discretion in the event of neutropenic fever/sepsis as per American Society of Clinical Oncology (ASCO) guidelines.16 Bone marrow aspiration and biopsy will be performed within 5 days of peripheral blood count recovery to an absolute neutrophil count (ANC) ≥ 1000/µL and platelets ≥ 100,000/µL without transfusions, or day 28 whichever comes first. If the peripheral blood absolute blast count is ≥ 5000/µL on day 21 of the first cycle, the second cycle may be administered immediately after bone marrow aspiration and biopsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient has unequivocal pathologic diagnosis of AML (≥ 20% blasts in the bone marrow based on World Health Organization (WHO) criteria), excluding acute promyelocytic leukemia t(15;17)(q22;q12); Promyelocytic leukemia gene (PML)- retinoic acid receptor alpha (RARA)
- •Age ≥ 65 years old
- •No prior treatment for AML except:
- •Emergency leukapheresis
- •Emergency treatment for hyperleukocytosis with hydroxyurea
- •Cranial radiotherapy (RT) for Central Nervous System (CNS) leukostasis (one dose only)
- •Growth factor/cytokine support
- •AML patients with therapy-related myeloid neoplasms are eligible if they have not received radiation therapy or chemotherapy (not including hormonal therapy) for their primary malignancy or disorder for ≥ 6 months. Hydroxyurea may be used at the investigator's discretion up to the first 28 days on Cycle 1 to maintain WBC <30,000/µl.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Subjects must have adequate hepatic and renal function
- •Female subject of child-bearing potential and male subjects with female partners of reproductive potential must use acceptable contraceptive methods
- •Able to understand and to provide written informed consent
- •Able to comply with all study procedures during the study including all visits and tests
- •Willing to adhere to the prohibitions and restrictions specified in this protocol
- •Patient must sign an informed consent form (ICF)
排除标准
- •Prior treatment with decitabine
- •Prior treatment with cytarabine
- •Prior treatment with pacritinib
- •Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
- •Active, uncontrolled, clinically significant infection(s)
- •Have other active malignancies (excluding other myeloid hematologic malignancies) or other malignancies within 12 months before enrollment, except curatively treated non-melanoma skin cancer, cervical intraepithelial neoplasia, organ-confined or treated non-metastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma
- •Are receiving any other investigational therapy or protocol-prohibited therapy
- •Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study
- •Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- •Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication
- •Inflammatory or chronic functional bowel disorder, such as Crohn's disease, inflammatory bowel disease, chronic diarrhea
- •Clinically symptomatic and uncontrolled cardiovascular disease
- •History of any of the following within 6 months: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure
- •New York Heart Association Class III or IV congestive heart failure
- •Patients with National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion with the approval of the investigator if the arrhythmias are stable, asymptomatic and unlikely to affect patient safety. Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade 3, corrected QT interval (QTc) prolongation >450 ms by Fridericia method, or other factors that increase the risk for QT prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 milliequivalent (mEq/L) that is persistent and refractory to correction], or family history of long QT interval syndrome).
研究组 & 干预措施
Arm A: Pacritinib and Decitabine
Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.
干预措施: Pacritinib (Drug)
Arm A: Pacritinib and Decitabine
Arm A: Each cycle: Decitabine 20mg/m2 intravenous daily for 10 days combined with ongoing pacritinib 200 mg twice daily.
干预措施: Decitabine (Drug)
Arm B: Pacritinib and Cytarabine
Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
干预措施: Pacritinib (Drug)
Arm B: Pacritinib and Cytarabine
Arm B: Each cycle: Cytarabine 20mg subcutaneous twice daily for 10 days combined with ongoing pacritinib 200mg twice daily.
干预措施: Cytarabine (Drug)
结局指标
主要结局
Complete Remission Rate
时间窗: 6 months
Complete remission rate is defined as number of subjects with complete remission according to the IWG criteria, which is defined by presence of \<5 percent of blasts in the bone marrow, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count \>1.0 x 109/L (1000/µL); platelet count \>100 x 109/L (100,000/µL); independence of red cell transfusions.
次要结局
- Event-free Survival(Time from entry on study until time at which there is treatment failure, AML relapse, or death from any cause, assessed throughout the study period up to 2 years)
- Overall Survival(2 years)
- Overall Remission Rate(6 months)
- Relapse-free Survival(From date of complete remission until either AML relapse or death from any cause, whichever came first, assessed throughout the study period up to 2 years)
- Time to Complete Response(From entry on study until complete remission, assessed throughout the study period up to 2 years)
- Remission Duration(time from complete remission to AML relapse, assessed throughout the study period up to 2 years.)