This multicenter, open-label, phase 1 study designed to evaluate safety and tolerability of multi-kinase inhibitor LNK01002 in patients with primary myelofibrosis (PMF), or MF due to polycythemia vera (PV-MF), or essential thrombocythemia (ET-MF), polycythemia vera (PV), or with acute myeloid leukemia (AML).
This is a Phase I, open-label, dose-finding study of the triple kinase inhibitor LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms. The study consists of two periods: the dose escalation, main period and a dose expansion period. In the dose escalation period, successive cohorts of patients with Malignant Myeloid Hematologic Neoplasms will be enrolled to establish the maximum tolerated dose. In the dose expansion period (dose-confirmation phase), three cohorts of patients will be enrolled: AML patients with confirmed FLT3-ITD mutations, AML patients without FLT3-ITD mutations, and patients with primary MF ,PV or PV/ET-MF. The safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms will be evaluated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
LNK01002 will be administrated orally.
Revive Research Institute
Farmington Hills, Michigan, United States
Revive Research Institute
Sterling Heights, Michigan, United States
Assessing the safety and tolerability of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms
Assessed by monitoring the frequency, duration and severity of adverse events and serious adverse events.
Time frame: 31 days
Assessing maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms
Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) will be assessed based on the safety profile by the SRC
Time frame: 31 days
Assessing the preliminary antitumor activity of LNK01002
The preliminary antitumor activity will be analyzed in patients with different types of malignant myeloid hematologic neoplasms by response rate using bone marrow and hematologic analyses (MF/AML) or by the MF Symptom Assessment Scale and spleen volume by MRI (MF).
Time frame: 24 Weeks
Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients
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Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15
Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Time frame: Day 1, Day 2, and Day 15