Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients

Phase 2

Completed

• Conditions: Acute Lymphoblastic Leukemia; Philadelphia Chromosome; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Mixed Phenotype Acute Leukemia
• Interventions: Drug: Azacitidine; Drug: Venetoclax; Drug: Flumatinib

• Registration Number: NCT05433532
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of azacitidine，venetoclax，and flumatinib in newly diagnosed Philadelphia chromosome-positive acute leukemia and accelerated phase or blast phase chronic myeloid leukemia patients.

Detailed Description

This is a phase Ⅱ, open-label, single-arm, single-center study in newly diagnosed Ph-positive acute leukemia and CML-AP/BP patients. The patients will receive azacitidine, venetoclax, and flumatinib regimen in the induction treatment. The patients who respond to induction treatment will undergo consolidation treatment, and an optional allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment with induction therapy according to patient's wishes.

Study Timeline

• Study Start: 2022-05-01
• Study First Submitted: 2022-06-14
• Study First Submitted QC: 2022-06-23
• Study First Posted: 2022-06-27
• Status Verified: 2024-04
• Primary Completion: 2024-04-13
• Study Completion: 2024-04-13
• Last Update Submitted: 2024-04-24
• Last Update Posted: 2024-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Newly diagnosed Ph-positive ALL/AML/MPAL and CML-AP/BP without the history of chemotherapy or target therapy.
2. Age 18-65.
3. Eastern Cooperative Oncology Group (ECOG) score: 0-3.
4. Total serum bilirubin ≤ 2 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 1.5 x ULN, aspartate aminotransferase (AST) ≤ 1.5 x ULN.
5. Creatinine clearance ≥ 30 mL/min.
6. Serum lipase ≤ 1.5 x ULN, amylase =< 1.5 x ULN.
7. No consumption of grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax.
8. Provide informed consent.

Exclusion Criteria

1. Patients with another malignant disease.
2. Patients has participated in or participating in other clinical trials.
3. Patients with uncontrolled active infection.
4. Patients with left ventricular ejection fraction < 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification.
5. Patients with HIV infection, active tuberculosis infection, or active hepatitis B or hepatitis C infection.
6. Patients with uncontrolled active bleeding.
7. Patients with history of previous chemotherapy or target therapy (except for oral hydroxyurea and/or leukopheresis for lowering white blood cell counts).
8. Pregnant and lactating women; patients of childbearing potential should be willing to practice methods of contraception throughout the study period.
9. Patients with other commodities that the investigators considered not suitable for the enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Azacitidine，Venetoclax，and Flumatinib Regimen	Azacitidine	See Detailed Description.
Azacitidine，Venetoclax，and Flumatinib Regimen	Venetoclax	See Detailed Description.
Azacitidine，Venetoclax，and Flumatinib Regimen	Flumatinib	See Detailed Description.

Primary Outcome Measures

Name	Time	Method
CMR	End of cycle 2 (each cycle is 28 days)	Complete molecular remission (CMR) was defined as undetectable BCR/ABL transcript.

Secondary Outcome Measures

Name	Time	Method
RFS	2 years	Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up.
CR/CRi, MRD-negative CR, CCyR, MMR	End of cycle 1 and 2 (each cycle is 28 days)	Complete remission (CR) was defined as \< 5% bone marrow blasts in an aspirate with spicules and independent of transfusions.; CR with incomplete hematologic recovery (CRi) was defined as \<5% bone marrow blasts, either ANC\<1×10\^9/L or platelets \< 100×10\^9/L, transfusion independence but with persistence of cytopenia.; Minimal residual disease (MRD)-negative CR was defined as a leukemic cell count below the sensitivity threshold of 1×10-4 (0.01%) bone marrow mononuclear cells (MNCs) by multiparameter flow cytometry.; Complete cytogenetic response (CCyR) was defined as lack of Ph in ≥ 20 bone marrow metaphases.; Major molecular response (MMR) was defined as a BCR-ABL/ABL transcript ratio of 0.1% (international scale).
Number of adverse events	End of cycle 1 and 2 (each cycle is 28 days)	Adverse events are evaluated with CTCAE V5.0.
OS	2 years	Overall survival (OS) was the time from enrollment to death for any reason.

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China