Chemotherapy-free Regimen of Venetoclax, Azacitidine Plus Orebatinib (VAO Regimen) for Newly Diagnosed ph+ALL

Phase 2

Recruiting

• Conditions: Ph-Positive Acute Lymphoblastic Leukemia
• Interventions: Drug: Venetoclax; Drug: Azacitidine; Drug: Orebatinib

• Registration Number: NCT06578546
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Venetoclax, Azacitidine Plus Orebatinib in newly diagnosed Philadelphia chromosome-positive Acute Lymphoblastic Leukemia.

Detailed Description

This is a phase Ⅱ, single-arm, open Label, multicenter clinical study in newly diagnosed Ph-positive acute lymphoblastic leukemia patients. The patients will receive venetoclax, azacitidine and orebatinib 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: 2024-02-01
• Status Verified: 2024-04
• Study First Submitted: 2024-04-27
• Study First Submitted QC: 2024-08-27
• Last Update Submitted: 2024-08-27
• Study First Posted: 2024-08-29
• Last Update Posted: 2024-08-29
• Primary Completion: 2025-02-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Newly diagnosed Ph-positive ALL without the history of chemotherapy or target therapy.
2. Age ≥18.
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. Provide informed consent.

Exclusion Criteria

1. Patients with another malignant disease.
2. Patients with uncontrolled active infection.
3. Patients with left ventricular ejection fraction < 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification.
4. Patients with HIV infection, active tuberculosis infection, or active hepatitis B or hepatitis C infection.
5. Patients with uncontrolled active bleeding.
6. Patients who has participated or participating in other clinical trials related to this disease.
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
Venetoclax, Azacitidine, and Orebatinib Regimen	Azacitidine	See Detailed Description.
Venetoclax, Azacitidine, and Orebatinib Regimen	Orebatinib	See Detailed Description.
Venetoclax, Azacitidine, and Orebatinib Regimen	Venetoclax	See Detailed Description.

Primary Outcome Measures

Name	Time	Method
complete molecular remission（CMR）	End of cycle 1 and 2 (each cycle is 28 days)	Proportion of patients achieving CMR at the end of 1 or 2 cycles

Secondary Outcome Measures

Name	Time	Method
CR	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.
CCyR	End of cycle 1 and 2 (each cycle is 28 days)	Complete cytogenetic response (CCyR) was defined as lack of Ph in ≥ 20 bone marrow metaphases.
MMR	End of cycle 1 and 2 (each cycle is 28 days)	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
RFS	1 year	Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up
OS	1 year	Overall survival (OS) was the time from enrollment to death for any reason.
CRi	End of cycle 1 and 2 (each cycle is 28 days)	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.
MRD-negative CR	End of cycle 1 and 2 (each cycle is 28 days)	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.

Trial Locations

Locations (1)

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