TGRX-678 Chinese Phase I in Chronic Myelogenous Leukemia (CML) Patients

NCT05434312 | Active Not Recruiting Phase 1

• 1 other identifier: TGRX-678-1001
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Myelogenous Leukemia

Outcome Measures

Primary Outcomes (4)

• Maximal tolerated dose (MTD)

  To determine the MTD of TGRX-678 in CML patients

  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

  At completion of the study, an average of 1.5 years

• Safety profile (DLT)

  to record and analyse subjects with dose-limiting toxicities (DLTs)

  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

  AE and SAE: through completion of the study, an average of 1.5 years

Secondary Outcomes (14)

• Hematologic Response

  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

  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

  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

  Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28

• Plasma Tmax

  Day 1, 7, 21, 28 of Cycle 1, Cycle 2 Day 28 and Cycle 3 Day 28

Study Arms (1)

TGRX-678

EXPERIMENTAL

Subjects to be treated with the investigational drug TGRX-678

Drug: TGRX-678

Interventions

TGRX-678 DRUG

Participants are given TGRX-678 tablets orally at one of the dose levels as pre-determined for the dose escalation sequence.

TGRX-678

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing to participate in the study with informed consent;
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shenzhen TargetRx, Inc.: lead
• Peking University People's Hospital: collaborator

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Qian Jiang, MD

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: June 28, 2022
• Study Start: March 29, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)