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

NCT ID: NCT06841952

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 158 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-15
• Study Completion Date: 2030-12-15

Brief Summary

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.

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) .

Conditions

AML, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ATRA+Venetoclax+Azacitidine

Intervention Type: DRUG

Participants will receive a standard dose of azacitidine (75mg/m²/day)，venetoclax (target dose, 400 mg)，ATRA 45mg/m²/day

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.

Group Type: ACTIVE_COMPARATOR

Chemotherapy drug

Intervention Type: DRUG

Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin).

Interventions

ATRA+Venetoclax+Azacitidine

Participants will receive a standard dose of azacitidine (75mg/m²/day)，venetoclax (target dose, 400 mg)，ATRA 45mg/m²/day

Intervention Type: DRUG

Chemotherapy drug

Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

HAN Yue

Chief of Service

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Countries

China

Central Contacts

Yue Han

Role: CONTACT

hanyuesz@163.com

86+0512-67781856

Chengyuan Gu

Role: CONTACT

guchengyuan@suda.edu.cn

86+18068016508

Facility Contacts

Xiang Zhang

Role: primary

zhuxiaomin@suda.edu.cn

86+0512-67781856

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

SOOCHOW-HY-2024-12-10

Identifier Type: -

Identifier Source: org_study_id