A Study of LNK01002 in Patients With Primary or Secondary Myelofibrosis,Polycythemia Vera or Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002 in Patients With Malignant Myeloid Hematologic Neoplasms

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04896112
• Other study ID #: LNK-1002-01
• Secondary ID: IND 153144
• Status: Withdrawn
• Phase: Phase 1
• Start date: April 8, 2021
• Est. completion date: October 20, 2022

Study information

• Verified date: June 2023
• Source: Lynk Pharmaceuticals Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 20, 2022
• Est. primary completion date: October 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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 exclusion criteria will be excluded from the

clinical study:

1. Allergic to any component of LNK01002.

2. Serum total bilirubin greater than 1.5 times the upper limit of the normal (ULN) reference range, except patients diagnosed as Gilbert's disease

3. ALT or AST higher than 3 times the ULN reference range without hepatic involvement by leukemia, which are excluded if higher than 5 times the ULN

4. Glomerular filtration rate or estimated creatinine clearance < 50 mL/min according to the Cockcroft-Gault formula;

5. Serum amylase or lipase levels higher than the ULN and considered clinically significant

6. International normalized ratio (INR) or partial activated prothrombin time (aPTT) above 1.5 times the ULN reference range

7. Known history of clinically significant liver disease, including viral or other hepatitis: a) Patients with hepatitis B or hepatitis C may be enrolled if they have a negative polymerase chain reaction (PCR)

8. Known human immunodeficiency virus (HIV) infection;

9. Clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina, coronary artery bypass surgery within 6 months before enrollment, congestive heart failure with New York Heart Association (NYHA) classification of III or above, left ventricular ejection fraction (LVEF) < 50%, or uncontrolled hypertension, cardiac arrhythmia;

10. Patients with history or presence of clinically relevant non-malignant CNS disease requiring treatment;

11. Patients who have received systemic antineoplastic therapy or radiotherapy within 2 weeks prior to start of study treatment;

12. Patients who have received hematopoietic stem cell transplantation (HSCT) within 60 days prior to the start of study treatment, or are receiving immunosuppressive therapy after HSCT at screening, or have graft-versus-host disease (GVHD) requiring ongoing treatment;

13. Received anti-tumor Chinese herbal medicine treatment within 1 week before the start of study treatment;

14. Received CYP3A strong inhibitors or strong inducers less than one week or 5 half-lives (whichever is longer) prior to the start of study treatment;

15. Uncontrolled, active infections requiring intravenous antibiotic treatment;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Polycythemia
• Polycythemia Vera
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• LNK01002
LNK01002 will be administrated orally.

Locations

Country	Name	City	State
United States	Revive Research Institute	Farmington Hills	Michigan
United States	Revive Research Institute	Sterling Heights	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Lynk Pharmaceuticals Co., Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	31 days
Primary	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	31 days
Primary	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).	24 Weeks
Secondary	Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15
Secondary	Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15
Secondary	Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15
Secondary	Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15
Secondary	Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15
Secondary	Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV,PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15
Secondary	Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV,PV-MF or ET-MF patients	Measurement will be using extensive PK sampling	Day 1, Day 2, and Day 15