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

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase Ⅱ, Open Label, Single Arm, Single-Center Study to Evaluate the Efficacy and Safety of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05433532
• Other study ID #: AZA+VEN+TKI
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2022
• Est. completion date: April 13, 2024

Study information

• Verified date: April 2024
• Source: The First Affiliated Hospital of Soochow University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 13, 2024
• Est. primary completion date: April 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Disease
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Mixed Phenotype Acute Leukemia
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Azacitidine
Azacitidine: 75mg/m2 qd, d1-d7, subcutaneous injection
• Venetoclax
Venetoclax: 100mg d1, 200mg d2, 300mg d3, 400mg d4-d14 or 21, oral (Adjusted according to the peripheral blood BCR/ABL1 results on day 14)
• Flumatinib
Flumatinib: 600mg qd, d4-d21, oral

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CMR	Complete molecular remission (CMR) was defined as undetectable BCR/ABL transcript.	End of cycle 2 (each cycle is 28 days)
Secondary	CR/CRi, MRD-negative CR, CCyR, MMR	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).	End of cycle 1 and 2 (each cycle is 28 days)
Secondary	Number of adverse events	Adverse events are evaluated with CTCAE V5.0.	End of cycle 1 and 2 (each cycle is 28 days)
Secondary	RFS	Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up.	2 years
Secondary	OS	Overall survival (OS) was the time from enrollment to death for any reason.	2 years