- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04896112
A Study of LNK01002 in Patients With Primary or Secondary Myelofibrosis,Polycythemia Vera or Acute Myeloid Leukemia
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Peter Langecker, M.D.
- Phone Number: 408-656-9855
- Email: plangecker@clinipace.com
Study Contact Backup
- Name: Sherry Weigand, M.D., Ph.D.
- Phone Number: 617-678-5412
- Email: sweigand1@lynkpharma.com
Study Locations
-
-
Michigan
-
Farmington Hills, Michigan, United States, 48334
- Revive Research Institute
-
Sterling Heights, Michigan, United States, 48314
- Revive Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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;
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patient with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 15 mg
Single dose of LNK01002 15 mg; followed by a 3-day observation period then 15mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 30 mg
LNK01002 30 mg twice daily (BID), followed by a 3-day observation period then 30 mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 60 mg
LNK01002 60 mg BID, followed by a 3-day observation period then 60 mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 100 mg
LNK01002 100 mg BID, followed by a 3-day observation period then 100 mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Acute Myeloid Leukemia With Mutant FLT3
LNK01002 at the RP2D dose in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms Without Mutant FLT3
LNK01002 at the RP2D dose in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 150 mg
LNK01002 150 mg BID, followed by a 3-day observation period then 150 mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 200 mg
LNK01002 200 mg BID, followed by a 3-day observation period then 200 mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Malignant Myeloid Hematologic Neoplasms treated with LNK01002 260 mg
LNK01002 260 mg BID, followed by a 3-day observation period then 260 mg BID in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
Experimental: Patients with Primary or Secondary Myelofibrosis,PV
LNK01002 at the RP2D dose in 28-day treatment cycles
|
LNK01002 will be administrated orally.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessing the preliminary antitumor activity of LNK01002
Time Frame: 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).
|
24 Weeks
|
Assessing the safety and tolerability of LNK01002 in patients with Malignant Myeloid Hematologic Neoplasms
Time Frame: 31 days
|
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
Time Frame: 31 days
|
Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) will be assessed based on the safety profile by the SRC
|
31 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measurement of pharmacokinetic (PK) parameter, AUC, in MF, PV,PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Measurement of pharmacokinetic (PK) parameter, Cmax, in MF, PV,PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Measurement of pharmacokinetic (PK) parameter, Tmax, in MF, PV, PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Measurement of pharmacokinetic (PK) parameter, CL/F, in MF, PV, PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Measurement of pharmacokinetic (PK) parameter, T1/2, in MF, PV, PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Measurement of pharmacokinetic (PK) parameter, Vz/F, in MF, PV,PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Measurement of pharmacokinetic (PK) parameter, MRT, in MF, PV,PV-MF or ET-MF patients
Time Frame: Day 1, Day 2, and Day 15
|
Measurement will be using extensive PK sampling
|
Day 1, Day 2, and Day 15
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Linda Wei, M.D., Lynk Pharmaceuticals Co., Ltd
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Bone Marrow Neoplasms
- Hematologic Neoplasms
- Primary Myelofibrosis
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Thrombocytosis
- Thrombocythemia, Essential
- Polycythemia Vera
- Polycythemia
Other Study ID Numbers
- LNK-1002-01
- IND 153144 (Registry Identifier: FDA)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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