Chiglitazar Sodium Combined With Venetoclax and Azacitidine (CVA) for the Treatment of R/R AML

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Relapse; Refractory AML
• Intervention / Treatment: Drug: CVA

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 If the disease still shows no improvement, they will be withdrawn from the clinical study and other treatment options will be considered, including allogeneic hematopoietic stem cell transplantation.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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bing Xu; Phone Number: 18750918842; Email: xubingzhangjian@126.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Bing Xu; Phone Number: 18750918842; Email: xubingzhangjian@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVA; Chiglitazar Sodium in combination with Venetoclax and Azacitidine	Drug: CVA; Chiglitazar Sodium in combination with Venetoclax and Azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate (CR)	The absolute neutrophil count is ≥1.0 × 10^3/μL, the platelet count is ≥1.0 × 10^5/μL, independent of red blood cell transfusions, and the percentage of bone marrow blasts is <5%. There are no circulating bone marrow blasts and blasts with Auer rods in the peripheral blood; no extramedullary disease is present.	Up to 36 months
Complete Remission with Incomplete Count Recovery (CRi)	Meeting all CR criteria except for residual neutropenia <1.0 × 10^3/μL (1000/μL) or thrombocytopenia <1.0 × 10^5/μL (100,000/μL). Dependence on red blood cell (RBC) transfusions is also defined as CRi.	Up to 36 months
Partial remission rate (PR)	Meets all hematological criteria for CR, but the percentage of blasts in the bone marrow aspirate sample has decreased by at least 50%, reaching between 5% and 25%.	Up to 36 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Xiamen University
• Investigators: Principal Investigator: Bing Xu, The First Aiffiliated hosptical of xiamen University

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 12, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: XMDYYYXYK-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No