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

NCT04896112 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: LNK-1002-01IND 153144
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

Acute Myeloid Leukemia; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Polycythemia Vera

Keywords

Malignant Myeloid Hematologic Neoplasms; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Myeloid malignancies; Myelofibrosis; Polycythemia Vera; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (7)

• Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients

  Day 1, Day 2, and Day 15

• Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients

  Day 1, Day 2, and Day 15

• Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients

  Day 1, Day 2, and Day 15

• Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients

  Day 1, Day 2, and Day 15

• Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients

  Day 1, Day 2, and Day 15

Study Arms (10)

Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg

EXPERIMENTAL

Single dose of LNK01002 15 mg; followed by a 3-day observation period then 15mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg

EXPERIMENTAL

LNK01002 30 mg twice daily (BID), followed by a 3-day observation period then 30 mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg

EXPERIMENTAL

LNK01002 60 mg BID, followed by a 3-day observation period then 60 mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg

EXPERIMENTAL

LNK01002 100 mg BID, followed by a 3-day observation period then 100 mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 150 mg

EXPERIMENTAL

LNK01002 150 mg BID, followed by a 3-day observation period then 150 mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 200 mg

EXPERIMENTAL

LNK01002 200 mg BID, followed by a 3-day observation period then 200 mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 260 mg

EXPERIMENTAL

LNK01002 260 mg BID, followed by a 3-day observation period then 260 mg BID in 28-day treatment cycles

Drug: LNK01002

Patients with Acute Myeloid Leukemia With Mutant FLT3

EXPERIMENTAL

LNK01002 at the RP2D dose in 28-day treatment cycles

Drug: LNK01002

Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3

EXPERIMENTAL

LNK01002 at the RP2D dose in 28-day treatment cycles

Drug: LNK01002

Patients with Primary or Secondary Myelofibrosis,PV

EXPERIMENTAL

LNK01002 at the RP2D dose in 28-day treatment cycles

Drug: LNK01002

Interventions

LNK01002 DRUG

LNK01002 will be administrated orally.

Also known as: LNK-1000318

Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg; Patients with Acute Myeloid Leukemia With Mutant FLT3; Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3; Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg; Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 150 mg; Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 200 mg; Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 260 mg; Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg; Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg; Patients with Primary or Secondary Myelofibrosis,PV

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 years old or older, male or female.
• Patients must have histologically or cytologically confirmed tumors of the following types.
• Dose Escalation Phase: Patients with PMF,PV/ET-MF,PV
• 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.
• Symptomatic splenomegaly
• 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
• Platelet count ≥ 100 × 10e9/L within 14 days before study drug administration
• Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L within 14 days before study drug administration
• 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.

You may not qualify if:

• Allergic to any component of LNK01002.
• Serum total bilirubin greater than 1.5 times the upper limit of the normal (ULN) reference range, except patients diagnosed as Gilbert's disease
• 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
• Glomerular filtration rate or estimated creatinine clearance \< 50 mL/min according to the Cockcroft-Gault formula;
• Serum amylase or lipase levels higher than the ULN and considered clinically significant
• International normalized ratio (INR) or partial activated prothrombin time (aPTT) above 1.5 times the ULN reference range
• 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)
• Known human immunodeficiency virus (HIV) infection;
• 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;
• Patients with history or presence of clinically relevant non-malignant CNS disease requiring treatment;
• Patients who have received systemic antineoplastic therapy or radiotherapy within 2 weeks prior to start of study treatment;
• 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;
• Received anti-tumor Chinese herbal medicine treatment within 1 week before the start of study treatment;
• 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;

Sponsors & Collaborators

• Lynk Pharmaceuticals Co., Ltd: lead

Study Sites (2)

Revive Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Revive Research Institute

Sterling Heights, Michigan, 48314, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Primary Myelofibrosis; Polycythemia Vera

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Study Officials

• Linda Wei, M.D.

  Lynk Pharmaceuticals Co., Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002

Study Record Dates

• First Submitted: May 8, 2021
• First Posted: May 21, 2021
• Study Start: April 8, 2021
• Primary Completion: October 20, 2022
• Study Completion: October 20, 2022
• Last Updated: June 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)