Study of Tretinoin Capsules in Combination With Azacitidine and Venetoclax in Treatment Naïve Participants With Acute Myeloid Leukemia

A Prospective, Two-arm, Multi-center Clinical Study of the Efficacy and Safety of Tretinoin Capsules Combined With Azacitidine and Venetoclax in Treatment Naïve Participants With Acute Myeloid Leukemia

This study was a prospective, two-arm, multicenter clinical trial to evaluate the efficacy and safety of tretinoin capsules combined with azacitidine and venetoclax in the treatment of newly diagnosed acute myeloid leukemia. Azacitidine, venetoclax, and tretinoin may arrest cancer cell growth by demethylation, promoting cell differentiation, or killing cells, while reducing blood-related adverse effects by promoting cell differentiation.

Study Overview

• Status: Not yet recruiting
• Conditions: AML, Adult
• Intervention / Treatment: Drug: ATRA+Venetoclax+Azacitidine; Drug: Chemotherapy drug

Detailed Description

This is a multi-center, non-controlled, open-label, Phase 3 interventional study.Young (≥18 and ≤60 years old) patients with newly diagnosed non M3, acute myeloid leukemia will receive a combination of AZA+Venetoclax+ATRA(AVA regimen) or daunorubicin +cytarabine(DA regimen) as induction treatment for 2 cycles.

According to standard procedures, patients will receive one of the following consolidation regimens separately, including the AVA regimen, or medium-dose cytarabine alone or in combination with anthracyclines regimen for 2cycle. After consolidation therapy, maintenance treatment could be given once a month for 4 times, then once every 3 months until progression.

After the second induction therapy, allogeneic hematopoietic stem cell transplantation was recommended for patients with suitable donors.

The primary endpoint is ORR after second induction therapy.Outcome measures included complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) .

• Study Type: Interventional
• Enrollment (Estimated): 158
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yue Han; Phone Number: 86+0512-67781856; Email: hanyuesz@163.com
• Study Contact Backup: Name: Chengyuan Gu; Phone Number: 86+18068016508; Email: guchengyuan@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Soochow University
      • Contact: Xiang Zhang; Phone Number: 86+0512-67781856; Email: zhuxiaomin@suda.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients initially diagnosed with AML (excluding APL) according to WHO diagnostic criteria.
• Patients who have not previously received other induction therapies (excluding hydroxyurea and leukapheresis).
• Total white blood cell (WBC) count ≤ 25 × 10^9/L.
• Ages 18 to 60 years, inclusive, with no gender restrictions.
• ECOG Performance Status score of 0-2.
• Total bilirubin ≤ 3 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) ≤ 3 times ULN; Aspartate aminotransferase (AST) ≤ 3 times ULN; (excluding leukemia infiltration).
• Endogenous creatinine clearance rate ≥ 30 ml/min.
• Enrolled patients must be capable of understanding and willing to participate in the study, and must sign the informed consent form.

Exclusion Criteria:

• Patients with Acute Promyelocytic Leukemia (APL).
• Patients with concomitant central nervous system leukemia or extramedullary leukemia involvement, such as testicular infiltration.
• Patients with current or historical immunodeficiency virus infection.
• Patients with active Hepatitis B or Hepatitis C infection.
• Patients with a history of drug allergy, including but not limited to etoposide, azacitidine, venetoclax, daunorubicin, and cytarabine.
• Patients with active or progressive malignant tumors or severe infections.
• Patients with a left ventricular ejection fraction (LVEF) of less than 30%, classified as New York Heart Association (NYHA) Class III or above, and those deemed ineligible for enrollment by the investigator.
• Patients who are pregnant or breastfeeding.
• Patients who refuse to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATRA+VEN+AZA arm; (1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 1 , 200mg orally for day 2, 300mg orally for day3-5, 400mg orally for day6-9,ATRA capsule 45mg/m² orally for day 11-28, every 28 days for 2 cycles or progression; (2)Consolidate therapy:AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 1 , 200mg orally for day 2, 300mg orally for day3-5, 400mg orally for day6-9,ATRA capsule 45mg/m² orally for day 11-28, every 28 days for 2 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 orally for d1-21 every 28 days,AZA 75mg/m² per day for days 1-7.Maintenance treatment was given once a month for 4 times, then once every 3 months until progression. After the second induction therapy, allogeneic hematopoietic stem cell transplantation was recommended for patients with suitable donors.	Drug: ATRA+Venetoclax+Azacitidine; Participants will receive a standard dose of azacitidine (75mg/m²/day)，venetoclax (target dose, 400 mg)，ATRA 45mg/m²/day
Active Comparator: DNR+ Ara-C arm; (1)Inductive therapy: Daunorubicin 60mg/m² d1-3，cytarabine100mg/m² d1-7, every 28 days for 2 cycles or progression; (2)Consolidate therapy:Intermediate-dose cytarabine alone or combined with anthracyclines is recommended (cytarabine 1.5-2g/m²), every 28 days for 2 cycles or till progression. (3) Maintenance therapy:AZA 75mg/m² per day for days 1-7 every 28 days.Maintenance treatment was given once a month for 4 times, then once every 3 months until progression. After the second induction therapy, allogeneic hematopoietic stem cell transplantation was recommended for patients with suitable donors.	Drug: Chemotherapy drug; Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall response rate (ORR) after the second therapy	ORR rate was defifined as patients achieving a CRc or PR	Efficacy was assessed within 2 weeks after completion of the second course of therapy or within 1 week before the third course of therapy
The composite complete remission rate (CRc) after the second therapy	complete response (CR) plus complete response with incomplete blood count recovery (CRi)] after 2 cycles of treatment.	Efficacy was assessed within 2 weeks after completion of the second course of therapy or within 1 week before the third course of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete response (CRc) after the first therapy	CRc rate was defifined as patients achieving a CR or CRi	Efficacy was assessed within 2 weeks after completion of the first course of induction therapy or within 1 week before the second course of therapy
The overall response rate (ORR) after the first therapy	ORR rate was defifined as patients achieving a CRc or PR	Efficacy was assessed within 2 weeks after completion of the first course of induction therapy or within 1 week before the second course of therapy
Rate of transfusion independence	Rate of transfusion independence (TI) , including platelet transfusion independence rate and red blood cell transfusion independence rate.	Up to 28 days after the start of therapy
Overall Survival (OS)	(OS) refers to the length of time from randomization until the death of the patient from any cause.	up to 2 years after the date of the last enrolled participants

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2025
• Primary Completion (Estimated): December 15, 2028
• Study Completion (Estimated): December 15, 2030

Study Registration Dates

• First Submitted: January 15, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: venetoclax; azacitidine; tretinoin
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Venetoclax; Azacitidine
• Other Study ID Numbers: SOOCHOW-HY-2024-12-10

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
• product manufactured in and exported from the U.S.: No