Venetoclax Combined With ATRA and ATO in Hyperleukocytic Acute Promyelocytic Leukemia

NCT07187505 | Active Not Recruiting DMC

• 1 other identifier: PJ 2025-03-57(1)
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the safety and effectiveness of combining venetoclax with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in patients with newly diagnosed acute promyelocytic leukemia (APL) who have very high white blood cell counts. APL is a rare type of blood cancer, and patients with high white blood cell levels often face serious complications. Current treatments with ATRA and ATO are effective, but the outcomes for patients with high white blood cells remain poor. This study will test whether adding venetoclax, a drug that helps leukemia cells die, can improve treatment results.

Conditions

Acute Promyelocytic Leukemia (APL)

Keywords

Venetoclax; All-Trans Retinoic Acid (ATRA); Arsenic Trioxide (ATO); Acute Promyelocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Early Mortality (Day 0-30)

  Proportion of patients who die from any cause within 30 days after treatment initiation.

  30 days

Secondary Outcomes (3)

• Incidence of Complications

  30 days

• Event-Free Survival (EFS)

  Up to 2 years

• Overall Response Rate (ORR)

  At 3 months after induction therapy

Other Outcomes (5)

• Changes in Daily White Blood Cell Count During Induction

  30 days

• Incidence of Laboratory Abnormalities

  From enrollment through 2 years.

• Incidence of Differentiation Syndrome

  30 days

Study Arms (1)

Experimental Arm: Venetoclax + ATRA + ATO

EXPERIMENTAL

Patients in this arm will receive a combination regimen consisting of venetoclax, all-trans retinoic acid (ATRA), and arsenic trioxide (ATO) as induction therapy, followed by consolidation according to protocol. The regimen is designed for newly diagnosed acute promyelocytic leukemia (APL) with hyperleukocytosis.

Drug: Venetoclax; Drug: All-trans retinoic acid; Drug: Arsenic Trioxide (ATO)

Interventions

Venetoclax DRUG

Venetoclax is a selective BCL-2 inhibitor administered orally once daily. The dose will be adjusted according to the study protocol and patient tolerance.

Also known as: Venclexta

Experimental Arm: Venetoclax + ATRA + ATO

All-trans retinoic acid DRUG

All-Trans Retinoic Acid (ATRA) is administered orally, twice daily, as part of standard induction and consolidation therapy for acute promyelocytic leukemia.

Also known as: Tretinoin, Vesanoid

Experimental Arm: Venetoclax + ATRA + ATO

Arsenic Trioxide (ATO) DRUG

Arsenic Trioxide (ATO) is administered intravenously once daily, in combination with ATRA and venetoclax, during induction and consolidation therapy.

Also known as: Trisenox

Experimental Arm: Venetoclax + ATRA + ATO

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with acute promyelocytic leukemia (APL) according to bone marrow morphology and immunophenotyping, consistent with the WHO 2016 diagnostic criteria.
• Age ≥14 years, both male and female patients are eligible.
• Adequate organ function, defined as:
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3 × upper limit of normal (ULN);
• Total serum bilirubin ≤1.5 × ULN;
• Creatinine clearance ≥30 mL/min;
• Serum cardiac enzymes \<2.0 × ULN.
• Signed informed consent obtained from the patient or a legally authorized representative.
• White blood cell (WBC) count \>10 × 10⁹/L at initial diagnosis, or WBC \>10 × 10⁹/L during treatment.

You may not qualify if:

• Diagnosis of acute non-promyelocytic leukemia, myeloid sarcoma, or chronic myeloid leukemia in accelerated or blast phase.
• Known hypersensitivity to any drug included in the study regimen.
• Pregnant or breastfeeding women, and women of childbearing potential who are unwilling to use effective contraception during the study treatment period.
• Presence of organic heart disease, such as uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months prior to screening that resulted in clinical symptoms or impaired cardiac function (NYHA class ≥III).
• Concurrent malignancies, except for:
• Malignancies treated with curative intent (e.g., hematopoietic stem cell transplantation) and with no known active disease for ≥5 years before enrollment;
• Adequately treated non-melanoma skin cancer or malignant lentigo without evidence of disease, even if diagnosed \<3 years before enrollment;
• Adequately treated carcinoma in situ without evidence of disease, even if diagnosed \<3 years before enrollment.
• Patients with acquired immunodeficiency syndrome (AIDS) or syphilis, or those with active hepatitis B (detectable HBV DNA) or active hepatitis C infection.
• Any concurrent medical condition or disease that may interfere with study procedures or outcomes, or that may pose an unacceptable risk to the participant as determined by the investigator (e.g., active systemic infection).
• Inability to understand or comply with the study protocol.
• Participation in another clinical study within 1 month prior to enrollment.

Sponsors & Collaborators

• Anhui Medical University: lead
• The First Affiliated Hospital of Anhui Medical University: collaborator

Study Sites (1)

Department of Hematology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road

Hefei, Anhui, 230022, China

Location

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

venetoclax; Tretinoin; Arsenic Trioxide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Zhangbiao Long

  The First Affiliated Hospital of Anhui Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2025
• First Posted: September 23, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The IPD and supporting documents will be available beginning 6 months after publication of the primary results and will remain available for 3 years.
• Access Criteria: Qualified researchers with a methodologically sound proposal may request access to the de-identified IPD and supporting documents. Requests should be submitted to the Principal Investigator by email. Proposals will be reviewed by the study steering committee, and access will be granted after approval and signing of a data access agreement.

Locations

CN (1)