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.
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. TERTIARY OBJECTIVES: I. To explore time to response (TTR) and duration of response (DOR). II. To explore the effect of the combination on anemia and transfusion dependence in patients with MF and MDS/MPN. III. To explore the impact of baseline mutational profile on International Working Group (IWG)-Myeloproliferative Neoplasms Research and Treatment (MRT) response and overall survival in patients with MF and MDS/MPN. IV. To explore the impact of baseline anemia on overall survival in patients with MF and MDS/MPN. OUTLINE: Patients are assigned to 1 of 2 treatment arms. ARM I (MF): Patients with MF receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28. Beginning course 4, patients also receive azacytidine subcutaneously (SC) or intravenously (IV) for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity. ARM II (MDS/MPN): Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I. After completion of study treatment, patients are followed up for 30 days and up to 5 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
121
M D Anderson Cancer Center
Houston, Texas, United States
Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis
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.
Time frame: Up to 24 weeks
Objective response rate (complete remission, partial remission, and hematologic improvement) in patients with myelodysplastic syndromes/myeloproliferative neoplasms
The method of Thall, Simon and Estey will be used for futility monitoring for this study.
Time frame: Up to 24 weeks
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
The method of Thall, Simon and Estey will be used for toxicity monitoring for this study.
Time frame: Up to 30 days after completion of study treatment
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