Clinical trial NCT06218771: A Study of TQB3454 Tablets in Patients With Blood Tumors
Official title: A Phase Ib Clinical Trial of TQB3454 Tablets in Patients With Blood Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-01-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to evaluate the safety of TQB3454 tablets in patients with acute myeloid leukemia and myelodysplastic syndrome, and determine the phase II recommended dose.


Eligibility criteria: Inclusion Criteria:

* Patients voluntarily joined the study and signed informed consent with good compliance.
* Men and women; The expected survival is ≥3 months.
* Negative serum/urine pregnancy test within 7 days prior to initial dose and must be non-lactating; Women of childbearing age agree to use contraception (such as an intrauterine device, birth control pill or condom) during the study and for six months after the study completion; Men agreed to use contraception during the study period and for six months after the end of the study.
* The major organs are functioning well;
* For Relapsing/refractory acute myeloid leukemia (AML):

  1. According to the classification criteria for Hematopoietic and lymphoid tissue tumors revised by the World Health Organization (WHO) in 2016, AML confirmed by bone marrow cell morphology, excluding acute promyelocytic leukemia (APL).
  2. ≥18 years old; Eastern Cooperative Oncology Group (ECOG) score is 0\~2.
  3. Blood biochemical examination:

  i: Total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN), liver infiltration ≤3×ULN in Gilbert syndrome patients or tumor diseases; ii: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; ALT and AST≤5×ULN if liver infiltration was associated.
* For myelodysplastic syndrome (MDS) with higher risk:

  1. MDS patients were confirmed by bone marrow cell morphology and cytogenetics and met the classification criteria of hematopoietic and lymphoid tissue tumors revised by WHO in 2016.
  2. ≥18 years old; ECOG score is 0\~2. c. Blood biochemical examination:

  i: Total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN), liver infiltration ≤3×ULN in Gilbert syndrome patients or tumor diseases.

ii: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; ALT and AST≤5×ULN if concomitant with liver infiltration.

Exclusion Criteria:

* Tumor diseases and history:

  1. The tumor has or is suspected to involve the central nervous system, or primary Central nervous system leukemia.
  2. Present or present with other malignant tumors within 3 years prior to the first dose. Except the following conditions: for other malignancies treated with a single operation, achieving a 5-year continuous disease-free survival (DFS); Cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor infiltrating basal membrane)\].
  3. Severe life-threatening complications of leukemia, such as uncontrolled bleeding, hypoxia or shock pneumonia, and disseminated intravascular coagulation.
* Previous antitumor therapy:

  1. Received National Medical Products Administration (NMPA) approved Chinese patent drugs with anticancer indications specified in the drug label within 2 weeks prior to initial administration.
  2. Toxicities associated with previous antineoplastic therapy did not return to CTCAE≤1, except for hair loss, fatigue and poor appetite.

     3. Associated diseases and history:

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  1. Abnormal liver.
  2. Renal abnormalities.
  3. Gastrointestinal abnormalities.
  4. Cardio-cerebrovascular abnormalities.
  5. Immune-related history.
  6. Lung disease.
  7. Comorbidities that were severe or poorly controlled and, in the investigator's judgment, significantly compromised patient safety or hindered study completion.
  8. Risk of bleeding.
* History of drug abuse or drug abuse.
* Participated in clinical trials of other drugs within the past 30 days;
* It is estimated that the patient's compliance to participate in this clinical study is insufficient.

Primary outcomes:
measure: The rate of all adverse events (AEs), serious adverse events (SAEs)
timeFrame: Up to 80 weeks
measure: The severity of all adverse events (AEs), serious adverse events (SAEs)
timeFrame: Up to 80 weeks
measure: Incidence of abnormal laboratory values
timeFrame: Up to 80 weeks
Secondary outcomes:
measure: Peak time (Tmax)
timeFrame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
measure: Peak concentration (Cmax)
timeFrame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
measure: Area under blood concentration-time curve (AUC 0-24h)
timeFrame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
measure: Steady-state apparent volume of distribution (Vz/F)
timeFrame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
measure: Steady-state blood trough concentration (Cmin,ss)
timeFrame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
measure: Complete response (CR) rate
timeFrame: Up to 80 weeks
measure: Complete response (CR) + Complete response with partial hematological recovery (CRh)
timeFrame: Up to 80 weeks
measure: Transfusion-independent improvement
timeFrame: Up to 80 weeks
measure: CR+CRh duration
timeFrame: Up to 80 weeks
measure: CR duration
timeFrame: Up to 80 weeks
measure: Duration of response (DOR)
timeFrame: Up to 80 weeks
measure: Time to CR+CRh
timeFrame: Up to 80 weeks
measure: Event-free survival (EFS)
timeFrame: Up to 80 weeks
measure: Overall survival (OS)
timeFrame: Up to 80 weeks
measure: Functional Assessment of Chronic Illness (FACIT) fatigue Scale
timeFrame: Up to 80 weeks
measure: Quality of life score
timeFrame: Up to 80 weeks
measure: Overall response rate (ORR)
timeFrame: Up to 80 weeks
measure: Progression-free survival (PFS)
timeFrame: Up to 80 weeks
measure: Leukemia-free survival
timeFrame: Up to 80 weeks
measure: Correlation between 2-hydroxyglutaric acid (2-HG) and efficacy
timeFrame: Pre-dose (baseline). Pre-dose on Cycle 1 Day 14, Cycle 1 Day 28, Cycle 2 Day 28, Cycle 3 Day 28, Cycle 4 Day 28, Cycle 5 Day 28, Cycle 6 Day 28, 28 days as a cycle
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Cangzhou
country: China
facility: Cangzhou people's Hospital
state: Hebei
city: Chengde
country: China
facility: The Affiliated Hospital of Chengde Medical College
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Wuxi
country: China
facility: Wuxi People's Hospital
state: Jiangsu
city: Binzhou
country: China
facility: Affiliated Hospital of Binzhou Medical College
state: Shandong
city: Yantai
country: China
facility: Yantai Mountain Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Hospital of Hematology, Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
References: