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

Primary Purpose

Acute Myeloid Leukemia, Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis

Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LNK01002
Sponsored by
Lynk Pharmaceuticals Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Malignant Myeloid Hematologic Neoplasms, Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Myeloid malignancies, Myelofibrosis, Polycythemia Vera, Acute Myeloid Leukemia

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.
  3. Dose Escalation Phase: Patients with PMF, PV/ET-MF

    1. Intermediate or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythaemia myelofibrosis which failed standard treatment.
    2. Symptomatic splenomegaly
    3. Not undergone splenectomy or splenic radiation therapy within 6 months prior to screening.
  4. Dose expansion phase: Patients with PMF, PV/ET-MF who relapsed or are intolerant to standard treatment, and relapsed/refractory AML
  5. Platelet count ≥ 100 × 10e9/L within 14 days before study drug administration
  6. Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L within 14 days before study drug administration
  7. 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 drug control:
  13. Received anti-tumor Chinese herbal medicine treatment within 1 week before the start of study treatment;
  14. Received CYP3A substrates, CYP2B6 substrates, CYP2C substrates, OATP1B3 substrates, UGT1A1 inhibitors, or UGT1A3 inhibitors 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;

Sites / Locations

  • Revive Research Institute
  • Revive Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 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 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 Acute Myeloid Leukemia With Mutant FLT3

Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3

Patients with Primary or Secondary Myelofibrosis,PV

Arm Description

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

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

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

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

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

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

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

LNK01002 at the RP2D dose in 28-day treatment cycles

LNK01002 at the RP2D dose in 28-day treatment cycles

LNK01002 at the RP2D dose in 28-day treatment cycles

Outcomes

Primary Outcome Measures

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.
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
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).

Secondary Outcome Measures

Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling
Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV,PV-MF or ET-MF patients
Measurement will be using extensive PK sampling

Full Information

First Posted
May 8, 2021
Last Updated
June 15, 2023
Sponsor
Lynk Pharmaceuticals Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04896112
Brief Title
A Study of LNK01002 in Patients With Primary or Secondary Myelofibrosis,Polycythemia Vera or Acute Myeloid Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Withdrawn
Why Stopped
sponsor decision
Study Start Date
April 8, 2021 (Actual)
Primary Completion Date
October 20, 2022 (Actual)
Study Completion Date
October 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lynk Pharmaceuticals Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of LNK01002
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg
Arm Type
Experimental
Arm Description
Single dose of LNK01002 15 mg; followed by a 3-day observation period then 15mg BID in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg
Arm Type
Experimental
Arm Description
LNK01002 30 mg twice daily (BID), followed by a 3-day observation period then 30 mg BID in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg
Arm Type
Experimental
Arm Description
LNK01002 60 mg BID, followed by a 3-day observation period then 60 mg BID in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg
Arm Type
Experimental
Arm Description
LNK01002 100 mg BID, followed by a 3-day observation period then 100 mg BID in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 150 mg
Arm Type
Experimental
Arm Description
LNK01002 150 mg BID, followed by a 3-day observation period then 150 mg BID in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 200 mg
Arm Type
Experimental
Arm Description
LNK01002 200 mg BID, followed by a 3-day observation period then 200 mg BID in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 260 mg
Arm Type
Experimental
Arm Description
LNK01002 260 mg BID, followed by a 3-day observation period then 260 mg BID in 28-day treatment cycles
Arm Title
Patients with Acute Myeloid Leukemia With Mutant FLT3
Arm Type
Experimental
Arm Description
LNK01002 at the RP2D dose in 28-day treatment cycles
Arm Title
Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3
Arm Type
Experimental
Arm Description
LNK01002 at the RP2D dose in 28-day treatment cycles
Arm Title
Patients with Primary or Secondary Myelofibrosis,PV
Arm Type
Experimental
Arm Description
LNK01002 at the RP2D dose in 28-day treatment cycles
Intervention Type
Drug
Intervention Name(s)
LNK01002
Other Intervention Name(s)
LNK-1000318
Intervention Description
LNK01002 will be administrated orally.
Primary Outcome Measure Information:
Title
Assessing the safety and tolerability of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms
Description
Assessed by monitoring the frequency, duration and severity of adverse events and serious adverse events.
Time Frame
31 days
Title
Assessing maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms
Description
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
Title
Assessing the preliminary antitumor activity of LNK01002
Description
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
Secondary Outcome Measure Information:
Title
Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15
Title
Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15
Title
Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15
Title
Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15
Title
Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15
Title
Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV,PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15
Title
Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV,PV-MF or ET-MF patients
Description
Measurement will be using extensive PK sampling
Time Frame
Day 1, Day 2, and Day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: Patients who meet any of the following exclusion criteria will be excluded from the clinical study: 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; Uncontrolled, active infections requiring intravenous antibiotic treatment;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linda Wei, M.D.
Organizational Affiliation
Lynk Pharmaceuticals Co., Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Revive Research Institute
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Revive Research Institute
City
Sterling Heights
State/Province
Michigan
ZIP/Postal Code
48314
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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