Chronic Myelogenous LeukemiaPhase 1NCT05434312
TGRX-678 Chinese Phase I in Chronic Myelogenous Leukemia (CML) Patients
A Phase 1 study testing TGRX-678 in people with Chronic Myelogenous Leukemia, run by Shenzhen TargetRx Co., Ltd. at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Myelogenous Leukemia
- What is being tested?
- TGRX-678
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 29 Mar 2021to Sep 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Peking University People's Hospital
Beijing, Beijing Municipality, 100044
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Myelogenous Leukemia
- Being tested
- TGRX-678
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TGRX-678Drug
Participants are given TGRX-678 tablets orally at one of the dose levels as pre-determined for the dose escalation sequence.
| Study group | Role | What they receive |
|---|---|---|
| TGRX-678 | Experimental | Subjects to be treated with the investigational drug TGRX-678 Receives: Drug: TGRX-678 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose (MTD)
To determine the MTD of TGRX-678 in CML patients
Measured: At end of Cycle 1 (each cycle is 28 days) when the posterior probability of DLT of a dose level is higher than 33%
Recommended phase II dose (RP2D)
To detemine the RP2D of TGRX-678 in CML patients for Phase II
Measured: At completion of the study, an average of 1.5 years
Safety profile (DLT)
to record and analyse subjects with dose-limiting toxicities (DLTs)
Measured: DLT: collect during Cycle 1 (28 days)
Safety profile (AEs/SAEs)
to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs), and
Measured: AE and SAE: through completion of the study, an average of 1.5 years
Secondary outcomes (14)
Hematologic Response
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.
Measured: at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
Cytogenetic Response
To record and analyse the cytogenetic response of subjects subjects will be determined whether partial or complete cytogenetic response (Ph+ < 35%) is reached.
Measured: at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
Molecular Response
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.
Measured: at screening period, weekly in Cycle 1, bi-weekly in Cycle 2 and monthly starting from Cycle 3 (each cycle is 28 days)
Plasma Cmax
Cmax of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Tmax
Tmax of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma T1/2
Half life of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma AUClast
AUClast of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma AUCinf
AUCinf of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Cmin
Cmin of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma AUCss
steady state AUC of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Cmax,ss
steady state Cmax of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Tmax,ss
steady state Tmax of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
CL
Clearance of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Vd
Volume of distribution of TGRX-678 as measured in plasma
Measured: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2022
- Study start29 Mar 2021
- Primary completionMar 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen TargetRx Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Peking University People's Hospital
- Responsible party
- Sponsor
- Investigators
- Qian Jiang, MD, Principal investigator, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05434312
- Sponsor's protocol ID
- TGRX-678-1001
- Status last verified
- Feb 2025
- First submitted
- 23 May 2022
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05434312
- Acronym / sponsor ID
- TGRX-678-1001
- Conditions
- Chronic Myelogenous Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Shenzhen TargetRx Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Peking University People's Hospital
- Study start
- 29 Mar 2021 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 28 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TGRX-678 | Experimental | Drug: TGRX-678Subjects to be treated with the investigational drug TGRX-678 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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;
Key exclusion criteria (19 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TGRX-678Participants are given TGRX-678 tablets orally at one of the dose levels as pre-determined for the dose escalation sequence. | Drug | TGRX-678 |
Primary outcome
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%
To determine the MTD of TGRX-678 in CML patients
Recommended phase II dose (RP2D)
Time frame: At completion of the study, an average of 1.5 years
To detemine the RP2D of TGRX-678 in CML patients for Phase II
Safety profile (DLT)
Time frame: DLT: collect during Cycle 1 (28 days)
to record and analyse subjects with dose-limiting toxicities (DLTs)
Safety profile (AEs/SAEs)
Time frame: AE and SAE: through completion of the study, an average of 1.5 years
to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs), and
14 secondary outcomes
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)
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)
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)
Plasma Cmax
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Tmax
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma T1/2
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma AUClast
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma AUCinf
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Cmin
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma AUCss
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Cmax,ss
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Plasma Tmax,ss
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
CL
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Vd
Time frame: Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Qian Jiang, MD principal investigator
Peking University People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TGRX-678 in people with Chronic Myelogenous Leukemia, run by Shenzhen TargetRx Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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%). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2025.