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

Official title

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

Overview

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) .

Interventions

• Drug ATRA+Venetoclax+Azacitidine
  Participants will receive a standard dose of azacitidine (75mg/m²/day)，venetoclax (target dose, 400 mg)，ATRA 45mg/m²/day
• Drug Chemotherapy drug
  Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin).

Primary outcome measures

• The overall response rate (ORR) after the second therapy [Time frame: 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 [Time frame: 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 (4)

• Composite complete response (CRc) after the first therapy [Time frame: 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 [Time frame: 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 [Time frame: Up to 28 days after the start of therapy]
• Overall Survival (OS) [Time frame: up to 2 years after the date of the last enrolled participants]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

China · 1 center

• The First Affiliated Hospital of Soochow University — Suzhou

Identifiers

NCT: NCT06841952 · SOOCHOW-HY-2024-12-10

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗