Evaluation of Ruxolitinib and Azacytidine Combination as a Therapy for Patients With Myelofibrosis and Myelodysplastic Syndrome/ Myeloproliferative Neoplasm
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 121
- 试验地点
- 1
- 主要终点
- Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis
研究概览
简要总结
This phase II trial studies how well ruxolitinib phosphate and azacytidine work in treating patients with myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacytidine, 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. Giving ruxolitinib phosphate and azacytidine may be an effective treatment for myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm.
详细描述
PRIMARY OBJECTIVES:
I. To determine the efficacy of the combination of RUX (ruxolitinib phosphate) with AZA (azacytidine) in patients with myelofibrosis (MF) (primary myelofibrosis, post polycythemia vera myelofibrosis, or post essential thrombocythemia myelofibrosis [PMF, post- PV MF, or post - ET MF]) in achieving objective improvements in disease status.
II. To determine the efficacy of the combination of RUX + AZA in patients with myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (breakpoint cluster region [BCR]-c-abl oncogene 1, non-receptor tyrosine kinase [ABL1] negative: aCML), and myelodysplastic syndromes/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U), in achieving objective improvements in disease status.
SECONDARY OBJECTIVES:
I. To determine the safety of the RUX + AZA combination in patients with MF and MDS/MPN.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patients with a diagnosis of primary myelofibrosis (PM), post polycythemia vera myelofibrosis (PPV MF), or post essential thrombocythemia myelofibrosis (PET MF) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to International Working Group (IWG-MRT) criteria
- •Patients with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) that require therapy
- •Understanding and voluntarily signing an Institutional Review Board (IRB)-approved informed consent form
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Direct bilirubin of =< 2 mg/dL
- •Serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) or 5 x ULN if related to MF or MDS/MPN associated liver infiltration
- •If total bilirubin is =< 2, fractionation is not required for eligibility determination
- •Creatinine =< 2.5 mg/dL
- •Platelets >= 50 x 10^9/L
- •Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
排除标准
- •For the MF and MDS/MPN-U arms (arms 1 & 2), use of any other standard drug (except hydroxyurea, anagrelide, growth factors, Revlimid, clofarabine, etc) or experimental drug or therapy within 14 days of starting study therapy
- •Patients previously treated with RUX or AZA (only applicable for the MF and MDS/MPN arms)
- •Any serious psychological condition or psychiatric illness that would prevent the subject from signing the informed consent document, in the investigator opinion
- •Pregnant or lactating females
- •Subjects of childbearing potential who are unwilling to take appropriate precautions (from screening through follow-up) to avoid becoming pregnant or fathering a child; females of non-childbearing potential are defined as women who a) are 55 years of age with history of amenorrhea for 1 year OR b) are surgically sterile for at least 3 months; for females of childbearing potential, or for males, pregnancy must be avoided by taking appropriate precautions; these precautions and the methods of contraception should be communicated to the subjects and their understanding confirmed
- •Any condition which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- •Known positive for human immunodeficiency virus (HIV) or with known active infectious hepatitis, type A, B or C
- •Patients with active malignancy of other type than required for this study, are not eligible with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast; patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received
研究组 & 干预措施
Arm I (MF patients)
Patients with MF receive ruxolitinib phosphate PO BID on days 1-28. Beginning course 4, patients also receive azacytidine SC or IV for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Azacitidine (Drug)
Arm I (MF patients)
Patients with MF receive ruxolitinib phosphate PO BID on days 1-28. Beginning course 4, patients also receive azacytidine SC or IV for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (MF patients)
Patients with MF receive ruxolitinib phosphate PO BID on days 1-28. Beginning course 4, patients also receive azacytidine SC or IV for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ruxolitinib Phosphate (Drug)
Arm II (MDS/MPN patients)
Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.
干预措施: Azacitidine (Drug)
Arm II (MDS/MPN patients)
Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (MDS/MPN patients)
Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.
干预措施: Ruxolitinib Phosphate (Drug)
结局指标
主要结局
Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis
时间窗: Up to 24 weeks
The method of Thall, Simon and Estey will be used for futility monitoring for this study. The objective response rate will be estimated along with the Bayesian 95% credible interval.
Objective response rate (complete remission, partial remission, and hematologic improvement) in patients with myelodysplastic syndromes/myeloproliferative neoplasms
时间窗: Up to 24 weeks
The method of Thall, Simon and Estey will be used for futility monitoring for this study.
次要结局
- Incidence of adverse events defined as grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is felt to be drug related as assessed by the Common Terminology Criteria for Adverse Events version 4.0(Up to 30 days after completion of study treatment)