A Clinical Trial to Evaluate the Safety and Tolerability of TQB3911 Tablets in Patients With BCR::ABL Fusion Gene Positive Leukemia

Official title

Phase I Clinical Trial to Evaluate the Safety and Tolerability of TQB3911 Tablets in Patients With BCR::ABL Fusion Gene Positive Leukemia

Overview

Phase I clinical trial to explore the safety, tolerability, and initial efficacy of TQB3911 tablets in BCR::ABL fusion gene positive leukemia.

Interventions

• Drug TQB3911 tablets
  TQB3911 is a small molecule BCR::ABL1 allosteric inhibitor. By occupying the myristyl binding site, TQB3911 recovers the inhibition of BCR::ABL1 fusion protein kinase activity, and ultimately inhibits the proliferation of tumor cells.

Primary outcome measures

• Phase II recommended doses (RP2D) [Time frame: Baseline up to 24 months]
• Dose-limiting toxicity (DLT) [Time frame: Up to 1 month]

Secondary outcome measures (10)

• Incidence and severity of adverse event (AE) and serious adverse event (SAE), and abnormal laboratory test indicators [Time frame: From the signing of informed consent for administration to 28 days after the last administration/start of the new antitumor therapy (whichever occurs first).]
• Peak time [Time frame: Single dose on days 1 to 3, day 8 of cycle 1, day 15 of cycle 1, day 22 of cycle 1, and day 2 to day 1, each cycle is 28 days.]
• C-QT Research [Time frame: Single dose: 1 hour, 0.5 hour, 10 minutes before dose and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 8 hours, 12 hours, 24 hours after dose.]
• Platelet count [Time frame: For the first six weeks, the assessment was weekly. Starting at week 6, assessments were performed at week 8 and every 4 weeks (±7 days) thereafter]
• The proportion of Philadelphia chromosomes in the metaphase of bone marrow cells [Time frame: They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks]
• Molecular reaction [Time frame: They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks]
• Progression free survival [Time frame: They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks]
• Overall survival [Time frame: They were evaluated every 12 weeks (±7 days) for 96 weeks and every 24 weeks (±7 days) after 96 weeks]
• Peak concentration Cmax [Time frame: Single dose on days 1 to 3, day 8 of cycle 1, day 15 of cycle 1, day 22 of cycle 1, and day 2 to day 1, each cycle is 28 days.]
• Plasma elimination half-life t1/2 [Time frame: Single dose on days 1 to 3, day 8 of cycle 1, day 15 of cycle 1, day 22 of cycle 1, and day 2 to day 1, each cycle is 28 days.]

Eligibility criteria

Inclusion criteria

• The subjects voluntarily joined the study, signed the informed consent, and had good compliance;
• Age: ≥18 years old (when signing the informed consent); Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-2; Expected survival of more than 3 months;
• During the screening period, the patients were identified as Chronic myelogenous leukemia-Chronic phase (CML-CP) or accelerated phase (AP) patients by bone marrow cell morphological examination, molecular biological examination or cytogenetic examination;
• Chronic myelogenous leukemia (CML) patients who are intolerant to Tyrosine kinase inhibitors (TKI) drugs or whose therapeutic effect is not satisfactory (that is, the therapeutic response evaluation result is failure)
• The main organs function well
• Female subjects of reproductive age should agree to use contraceptives (such as Iuds, contraceptives, or condoms) during the study period and for 6 months after the end of the study; Have a negative serum pregnancy test within 7 days prior to study enrollment and must be a non-lactating subject; Male subjects should agree to use avoidance during the study period and for 6 months after the end of the study period.

Exclusion criteria

• Had or was currently suffering from other malignant tumors within 5 years before the first medication
• Combined with active central nervous system leukemia
• Major surgical treatment and significant traumatic injury were received within 28 days before the start of study treatment
• Previous history of myocardial infarction, pulmonary hypertension, or angina pectoris within 3 months before the first medication, or clinically significant arrhythmias such as ventricular tachycardia, complete left bundle branch block, and high atrioventricular block
• Acute pancreatitis and a history of chronic pancreatitis within 12 months before the first medication
• History of interstitial lung disease, radiation pneumonia requiring steroid treatment, or drug-related pneumonia
• Patients with CML-CP who have achieved complete cytogenetic response (CCyR)
• Received live attenuated vaccine within 4 weeks before the first dose, or planned to receive live attenuated vaccine during study participation
• Use of drugs that may have caused QT prolongation or tip torsical tachycardia in the 7 days prior to initial administration, or continuation of these medications during the study period

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 5 centers

• Peking University People's Hospital — Beijing
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• Henan Cancer Hospital — Zhengzhou
• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai
• The First Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT06672263 · TQB3911-I-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗