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

Primary Purpose

Philadelphia Chromosome, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Azacitidine
Venetoclax
Flumatinib
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Philadelphia Chromosome focused on measuring Ph-positive AL, CML-AP/BP, Azacitidine+Venetoclax+Flumatinib

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Azacitidine，Venetoclax，and Flumatinib Regimen

Arm Description

See Detailed Description.

Outcomes

Primary Outcome Measures

CMR
Complete molecular remission (CMR) was defined as undetectable BCR/ABL transcript.

Secondary Outcome Measures

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).
Number of adverse events
Adverse events are evaluated with CTCAE V5.0.
RFS
Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up.
OS
Overall survival (OS) was the time from enrollment to death for any reason.

Full Information

First Posted
June 14, 2022
Last Updated
November 27, 2022
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT05433532
Brief Title
Study of Azacitidine，Venetoclax，and Flumatinib in Newly Diagnosed Ph-positive Acute Leukemia and CML-AP/BP Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2022 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Philadelphia Chromosome, Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia, Mixed Phenotype Acute Leukemia
Keywords
Ph-positive AL, CML-AP/BP, Azacitidine+Venetoclax+Flumatinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Azacitidine，Venetoclax，and Flumatinib Regimen
Arm Type
Experimental
Arm Description
See Detailed Description.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Intervention Description
Azacitidine: 75mg/m2 qd, d1-d7, subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Flumatinib
Intervention Description
Flumatinib: 600mg qd, d4-d21, oral
Primary Outcome Measure Information:
Title
CMR
Description
Complete molecular remission (CMR) was defined as undetectable BCR/ABL transcript.
Time Frame
End of cycle 2 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
CR/CRi, MRD-negative CR, CCyR, MMR
Description
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).
Time Frame
End of cycle 1 and 2 (each cycle is 28 days)
Title
Number of adverse events
Description
Adverse events are evaluated with CTCAE V5.0.
Time Frame
End of cycle 1 and 2 (each cycle is 28 days)
Title
RFS
Description
Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up.
Time Frame
2 years
Title
OS
Description
Overall survival (OS) was the time from enrollment to death for any reason.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Newly diagnosed Ph-positive ALL/AML/MPAL and CML-AP/BP without the history of chemotherapy or target therapy. Age 18-65. Eastern Cooperative Oncology Group (ECOG) score: 0-3. Total serum bilirubin ≤ 2 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 1.5 x ULN, aspartate aminotransferase (AST) ≤ 1.5 x ULN. Creatinine clearance ≥ 30 mL/min. Serum lipase ≤ 1.5 x ULN, amylase =< 1.5 x ULN. No consumption of grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days prior to starting venetoclax. Provide informed consent. Exclusion Criteria: Patients with another malignant disease. Patients has participated in or participating in other clinical trials. Patients with uncontrolled active infection. Patients with left ventricular ejection fraction < 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification. Patients with HIV infection, active tuberculosis infection, or active hepatitis B or hepatitis C infection. Patients with uncontrolled active bleeding. Patients with history of previous chemotherapy or target therapy (except for oral hydroxyurea and/or leukopheresis for lowering white blood cell counts). Pregnant and lactating women; patients of childbearing potential should be willing to practice methods of contraception throughout the study period. Patients with other commodities that the investigators considered not suitable for the enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaowen Tang, Ph.D
Phone
67781525
Email
xwtang1020@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Depei Wu, Ph.D
Phone
67781856
Email
drwudepei@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaowen Tang, Ph.D
Organizational Affiliation
The First Affiliated Hospital of Soochow University
Official's Role
Study Chair
Facility Information:
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaowen Tang, Ph.D
Phone
67781525
Email
xwtang1020@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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

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