Clinical trial NCT06737523: Chiglitazar Sodium Combined With Venetoclax and Azacitidine (CVA) for the Treatment of R/R AML
Official title: A Multicenter, Prospective, Single-arm Clinical Study of Chiglitazar Sodium Combined With Venetoclax and Azacitidine (CVA) for the Treatment of Refractory/Relapsed Acute Myeloid Leukemia (R/R AML)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Relapse
Refractory AML
Lead sponsor: The First Affiliated Hospital of Xiamen University
Sponsor class: OTHER
First posted: 2024-12-17
Enrollment: 30
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: To investigate the safety and efficacy of the CVA regimen, composed of Chiglitazar Sodium in combination with Venetoclax and Azacitidine, in the treatment of patients with refractory/relapsed acute myeloid leukemia (R/R AML).

Detailed description: 1. Sogletanib 48mg per dose, once daily; Venetoclax 400mg per dose, once daily for 4 weeks; Azacitidine 100mg, once daily, days 1-7. 28 days/cycle, at least 2 cycles.
2. The drug concentration of Venetoclax will be tested one week after oral administration, and the dose will be adjusted according to the concentration.
3. After 2 treatment courses, patients with stable disease (SD) or progressive disease (PD) may receive up to 1-2 additional courses. If the disease still shows no improvement, they will be withdrawn from the clinical study and other treatment options will be considered, including allogeneic hematopoietic stem cell transplantation.

Note: In special circumstances based on the patient's condition, laboratory test indicators, and adverse reactions, etc.; for Venetoclax dosage, if the white blood cell count is \>25×10\^9/L before administration, hydroxyurea may be given first to reduce the count to less than 25×10\^9/L before adding Venetoclax, and then the concentration of Venetoclax will be tested and the dose adjusted according to the concentration.

Eligibility criteria: Inclusion Criteria:

1. Acute myeloid leukemia (AML) confirmed by histology. Relapsed or refractory AML, including: a) Refractory disease is defined as no remission after at least one prior treatment. b) Disease relapse is defined as 5% or more blasts in the bone marrow after remission. c) Patients with AML arising from myelodysplastic syndromes (including CMML) or myeloproliferative neoplasms (secondary AML, t-AML) are also eligible;
2. Age ≥18 years, male or female, with an expected survival of more than 3 months;
3. Estimated creatinine clearance ≥ 50 mL/min;
4. AST and ALT ≤ 3.0 x ULN (unless considered due to leukemia organ involvement), bilirubin ≤ 3.0 x ULN (unless considered due to leukemia organ involvement);
5. ECOG ≤ 2;
6. Subjects are non-pregnant or using contraceptive measures during treatment;
7. Capable of understanding and voluntarily providing informed consent.

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL);
2. Active central nervous system leukemia;
3. Patients with clinically significant QTc interval prolongation (males \> 450 ms; females \> 470 ms), ventricular tachycardia and atrial fibrillation, second-degree heart block, history of myocardial infarction and congestive heart failure within the year prior to enrollment, and patients with clinically symptomatic coronary heart disease requiring medication;
4. Active, uncontrolled severe infection;
5. Other non-myeloid malignancies within the past 2 years;
6. Mental disorders that would impede study participation;
7. Previous solid organ transplantation (pre-treatment with SCT is allowed, but not allowed if the patient has GVHD or is still receiving immunosuppressive/GVHD treatment);
8. Any other conditions that, in the opinion of the investigator, make the patient unsuitable to participate in this trial.

Primary outcomes:
measure: Complete remission rate (CR)
timeFrame: Up to 36 months
measure: Complete Remission with Incomplete Count Recovery (CRi)
timeFrame: Up to 36 months
measure: Partial remission rate (PR)
timeFrame: Up to 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
Study officials:
affiliation: The First Aiffiliated hosptical of xiamen University
name: Bing Xu
role: PRINCIPAL_INVESTIGATOR
References: