The purpose of this research is to study the safety and tolerability and to establish the maximum tolerated dose (MTD) of the combination of two drugs, fedratinib and decitabine, for the treatment of advanced-phase MPNs.
This is a single center phase I dose-escalation trial of Fedratinib in Combination with Decitabine in Patients with Myeloproliferative Neoplasms. The primary objective is to determine the maximum tolerated dose of the combination therapy, using a 3+3 dose escalation algorithm. Fedratinib will be administered at 2 dose levels: 300 mg and 400 mg by mouth, once daily. Fedratinib will be administered concomitantly with decitabine 20 mg/m2 intravenously over 1 hour per day for 5 days in 28-day cycles.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
300 mg by mouth, once daily
20 mg/m2 for injection, for intravenous use
400 mg by mouth, once daily
New York Presbyterian Hospital/Columbia University Irving Medical Center
New York, New York, United States
Maximum Tolerated Dose (MTD) of Decitabine and Fedratinib
The MTD will be determined using a 3+3 algorithm. If \< 33% of the subjects enrolled at a dose level experience a dose-limiting toxicity (DLT), escalation to the next designated dose cohort will continue. If ≥ 33% of the subjects enrolled at a dose level experience a DLT, the previous dosing cohort will be considered the MTD. DLT is defined as: (1) Grade 3, 4, or 5 non-hematologic toxicity considered at least possibly related to the study drug, except for infection, bleeding, fever, fatigue, dyspnea, and (2) Grade 3, 4, or 5 anemia, neutropenia or thrombocytopenia with a hypocellular bone marrow and \< 5% marrow blasts lasting for 42 days or more.
Time frame: Up to 8 weeks for each dosing cohort
Complete Remission (CR) Rate
Complete remission defined as participants that are free of all symptoms related to leukemia and have an absolute neutrophil count ≥ 1 x 10\^9/L, no need for red blood cell transfusion, platelet count ≥ 100 x 10\^9/L, and normal marrow differential (≤ 5 % blasts) in a normo- or hypercellular marrow.
Time frame: Up to 3 years
Composite Complete Remission (CRc) Rate
CRc defined as (CR + Complete remission with incomplete count recovery (CRi)). CRi defined as CR but incomplete count recovery (absolute neutrophil count \< 1000/microL or platelet count \< 100,000/micro/L).
Time frame: Up to 3 years
Partial Remission (PR) Rate
PR defined as CR with 6 - 25 % abnormal cells in the marrow or 50 % decrease in bone marrow blasts.
Time frame: Up to 3 years
Progression Free Survival (PFS)
PFS is defined as the duration of time from entry on study to time of recurrence, flow cytometric relapse, cytogenetic relapse, molecular relapse, or death, whichever occurs first.
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Time frame: Up to 3 years
Overall Survival (OS)
OS is defined as the duration of time from entry on study to time of death from any cause.
Time frame: Up to 3 years