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

NCT06841952 | Not Yet Recruiting

• 1 other identifier: SOOCHOW-HY-2024-12-10
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

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.

Conditions

AML, Adult

Keywords

tretinoin; azacitidine; venetoclax

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Composite complete response (CRc) after the first therapy

  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

  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

  Up to 28 days after the start of therapy

• Overall Survival (OS)

  up to 2 years after the date of the last enrolled participants

Study Arms (2)

ATRA+VEN+AZA arm

EXPERIMENTAL

(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

DNR+ Ara-C arm

ACTIVE COMPARATOR

(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

Interventions

ATRA+Venetoclax+Azacitidine DRUG

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

ATRA+VEN+AZA arm

Chemotherapy drug DRUG

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

DNR+ Ara-C arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Yue Han

CONTACT

86+0512-67781856; hanyuesz@163.com

Chengyuan Gu

CONTACT

86+18068016508; guchengyuan@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Service

Study Record Dates

• First Submitted: January 15, 2025
• First Posted: February 24, 2025
• Study Start: February 15, 2025
• Primary Completion (Estimated): December 15, 2028
• Study Completion (Estimated): December 15, 2030
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)