- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05434312
TGRX-678 Chinese Phase I in Chronic Myelogenous Leukemia (CML) Patients
February 27, 2024 updated by: Shenzhen TargetRx, Inc.
A Single-arm, Open-label, Dose Escalation and Dose Expansion Phase 1 Trial to Determine the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TGRX-678 in Patients With Refractory or Advanced CML
The purpose of this single- arm, open-lable, dose escalation + dose expansion study is to evalulate the safety, tolerability, pharmacokinetic and preliminary efficacy of TGRX-678 in Chronic Myelogenous Leukemia patients who had failure with or are intolerant to TKI treatments.
Study Overview
Detailed Description
This is the first-in-human trial with TGRX-678 which aims to evaluate the safety profile and preliminary efficacy profile in advanced or refractory CML patients with previous failure or intolerence to TKI treatments.
The primary purpose of this study is to evaluate the safety profile of TGRX-678, including determination of the maximal tolerated dose (MTD) and recommended phase II dose (RP2D), and other safety measures of the investigational drug, such as adverse events and abnormal clinical outcomes.
Preliminary efficacy profile of TGRX-678 is evaluated based on the changes in peripheral blood cells and disease-associated cytogenetic markers.
The safety, tolerability and efficacy profiles, along with pharmacokinetic analysis, will be assessed together to determine the optimal dose for expansion.
Study Type
Interventional
Enrollment (Estimated)
90
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Kai Yan
- Phone Number: 86-13754709367
- Email: kai.yan@tjrbiosciences.com
Study Locations
-
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Beijing
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Beijing, Beijing, China, 100044
- Recruiting
- Peking University People's Hospital
-
Contact:
- Qian Jiang, MD
- Phone Number: 010-88326666
- Email: Jiangqian@medmail.com
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Principal Investigator:
- Qian Jiang, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Willing to participate in the study with informed consent;
- 18-75 years of age at the time of screening;
- Male or female;
- Diagnosis of CML-CP by cytomorphological examination of the bone marrow, molecular biology examination, or cytogenetic testing during the screening period (according to the NCCN guidelines (NCCN, 2021);
- Received prior treatment with imatinib, dasatinib or nilotinib; patients must be intolerant or resistant to the above drugs according to MD Anderson or ELN guidelines;
- ECOG performance status ≤ 2;
- Minimum life expectancy of 3 months;
- Adequate renal function, defined as serum creatinine <1.5× upper limit of normality (ULN)
- Adequate liver function, defined as total bilirubin <1.5× ULN, AST and ALT <2.5×ULN; if liver function is compromised due to CML, AST and ALT <5×ULN;
- Adequate coagulation function, defined as PT<1.5×ULN, INR<1.5×ULN, and APTT<1.5×ULN;
- Normal pancreatic function, defined as lipase and amylase <1.5× ULN;
- Normal QTc interval, defined as ≤450 ms in males and ≤470 ms in females, as indicated by ECG screening results;
- For women with child-bearing potential, negative pregnancy test result at screening period;
- Pregnant or breast feeding and female patients of childbearing potential must agree to use effective methods of contraception.
Exclusion Criteria:
- Received TKI treatment within 7 days of first dosing of the investigational drug, or AEs related to previous treatment has not been recovered to Grade 1 or lower (except for alopecia);
- Exposure to other antineoplastic therapies and either of the following: hydroxyurea or anagrelide within 24 h prior to the first dose; interferon or immunotherapy within 14 days prior to the first dose, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy (excluding any TKI therapy) within 28 days prior to the first dose;
- Stem cell transplant < 60 days prior to the first dose, with evidence of graft versus host disease (GVHD) or GVHD requiring immunosuppressive therapy;
- Concomitant immunosuppressive therapy (other than short term corticosteroid treatment);
- Exposure to drugs related to torsade de pointes within 1 month of the screening period;
- Cytological or pathological diagnosis of active central nervous system disorder;
- CML-CP patients already achieved complete cytogenetic response;
- CML-AP patients already achieved major hematological response;
- Significant uncontrolled cardiac disease;
- Uncontrolled hypertension (Diastolic BP > 85mm Hg; Systolic > 145 mm Hg; achieved with or without medication);
- Exposure to herbal preparations or over-the-counter medications containing herbal ingredients within 2 weeks prior to the first dose;
- Severe hemorrhagic disorders unrelated to CML;
- History of grade 3-4 pancreatitis or history of alcohol abuse;
- Uncontrolled hyper-triglyceridemia (TG>450 mg/dL);
- Malabsorption syndrome or other illness that could affect oral absorption;
- Diagnosis of another primary malignancy in the past 3 years (other than non-melanoma skin cancer, cervical carcinoma in situ, or controlled prostate cancer that have been cured within 3 years;
- Invasive/extensive surgery within 14 days prior to initiating TGRX-678 therapy;
- Active clinically significant infections, including syphilis, HIV, Hepatitis B or Hepatitis C;
- Other criteria in the opinion of the investigator or the medical monitor that is unsuitable for the study, including diseases that could compromise the patients safety or the evaluation of the drugs safety or poor compliance.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TGRX-678
Subjects to be treated with the investigational drug TGRX-678
|
Participants are given TGRX-678 tablets orally at one of the dose levels as pre-determined for the dose escalation sequence.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximal tolerated dose (MTD)
Time Frame: At end of Cycle 1 (each cycle is 28 days) when the posterior probability of DLT of a dose level is higher than 33%
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To determine the MTD of TGRX-678 in CML patients
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At end of Cycle 1 (each cycle is 28 days) when the posterior probability of DLT of a dose level is higher than 33%
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Recommended phase II dose (RP2D)
Time Frame: At completion of the study, an average of 1.5 years
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To detemine the RP2D of TGRX-678 in CML patients for Phase II
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At completion of the study, an average of 1.5 years
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Safety profile (DLT)
Time Frame: DLT: collect during Cycle 1 (28 days)
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to record and analyse subjects with dose-limiting toxicities (DLTs)
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DLT: collect during Cycle 1 (28 days)
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Safety profile (AEs/SAEs)
Time Frame: AE and SAE: through completion of the study, an average of 1.5 years
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to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs), and
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AE and SAE: through completion of the study, an average of 1.5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hematologic Response
Time Frame: at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
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To record and analyse the hematologic response of subjects.
Subjects will be determined whether complete hematologic response (CHR) or no evience of leukemia (NEL) is reached.
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at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
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Cytogenetic Response
Time Frame: at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
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To record and analyse the cytogenetic response of subjects subjects will be determined whether partial or complete cytogenetic response (Ph+ < 35%) is reached.
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at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
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Molecular Response
Time Frame: at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
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To record and analyse the molecular response of subjects Subjects will be detmined whether major molecular response (BCR-ABL1 (IS) no more than 0.1%) is reached.
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at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
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Plasma Cmax
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Cmax of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma Tmax
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Tmax of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma T1/2
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Half life of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma AUClast
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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AUClast of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma AUCinf
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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AUCinf of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma Cmin
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Cmin of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma AUCss
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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steady state AUC of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma Cmax,ss
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
|
steady state Cmax of TGRX-678 as measured in plasma
|
Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Plasma Tmax,ss
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
|
steady state Tmax of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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CL
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Clearance of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Vd
Time Frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Volume of distribution of TGRX-678 as measured in plasma
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Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Qian Jiang, MD, Peking University People's Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 29, 2021
Primary Completion (Estimated)
December 31, 2024
Study Completion (Estimated)
June 30, 2025
Study Registration Dates
First Submitted
May 23, 2022
First Submitted That Met QC Criteria
June 21, 2022
First Posted (Actual)
June 28, 2022
Study Record Updates
Last Update Posted (Estimated)
February 29, 2024
Last Update Submitted That Met QC Criteria
February 27, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TGRX-678-1001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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