Acute Myeloid Leukemia, Polycythemia Vera, Post-essential Thrombocythemia Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Primary Myelofibrosis
Conditions
Keywords
Malignant Myeloid Hematologic Neoplasms, Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Myeloid malignancies, Myelofibrosis, Polycythemia Vera, Acute Myeloid Leukemia
Brief summary
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).
Detailed description
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.
Interventions
DRUGLNK01002
LNK01002 will be administrated orally.
Sponsors
Lynk Pharmaceuticals Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age: 18 years old or older, male or female. 2. Patients must have histologically or cytologically confirmed tumors of the following types. * Dose Escalation Phase: Patients with PMF,PV/ET-MF,PV 1. Intermediate or high-risk primary myelofibrosis, intermediate or high-risk post-polycythemia vera myelofibrosis , or post-essential thrombocythemia myelofibrosis , or high-risk polycythemia vera who have no available therapy or relapsed after allogeneic hematopoietic cell transplantation. 2. Symptomatic splenomegaly 3. Not undergone splenectomy or splenic radiation therapy within 6 months prior to screening. * Dose expansion phase: Patients with PMF, PV/ET-MF,PV who relapsed or are intolerant to standard treatment, and relapsed/refractory AML 3. Platelet count ≥ 100 × 10e9/L within 14 days before study drug administration 4. Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L within 14 days before study drug administration 5. Women of childbearing potential negative pregnancy test at screening. Female patients of childbearing potential, or male patients and their partners should agree to effective contraception from signing ICF until 6 months after the last dose of study drug.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessing the safety and tolerability of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms | 31 days | Assessed by monitoring the frequency, duration and severity of adverse events and serious adverse events. |
| Assessing maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms | 31 days | Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) will be assessed based on the safety profile by the SRC |
| Assessing the preliminary antitumor activity of LNK01002 | 24 Weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
| Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
| Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
| Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV,PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
| Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV,PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
| Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
| Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients | Day 1, Day 2, and Day 15 | Measurement will be using extensive PK sampling |
Countries
United States
Outcome results
None listed