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

Soochow University

Status: Not yet enrolling

Conditions: AML, Adult

Treatments: Drug: Chemotherapy drug; Drug: ATRA+Venetoclax+Azacitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT06841952

SOOCHOW-HY-2024-12-10

Details and patient eligibility

About

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.

Full 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) .

Enrollment: 158 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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158 participants in 2 patient groups

ATRA+VEN+AZA arm

Experimental group

Description:

(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.

Treatment:

Drug: ATRA+Venetoclax+Azacitidine

DNR+ Ara-C arm

Active Comparator group

Description:

(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.

Treatment:

Drug: Chemotherapy drug