Venetoclax Combined with Intensive Therapy for Acute Myeloid Leukemia Patients with Lower Early Peripheral Blast Clearance Rate After Standard Induction Therapy

Registration Number
NCT06643962
Lead Sponsor
Affiliated Hospital of Nantong University
Brief Summary

This single-center prospective cohort study aims to evaluate the efficacy and safety of Intensifying treatment with Venetoclax along with intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) except acute promyelocytic leukemia (non-APL) and exhibiting lower early peripheral blast clearance rate (EPBCR) after standard Intensive...

Detailed Description

This is a single-center, prospective cohort study for the intensifying treatment with venetoclax on the standard 3+7 regimen in newly diagnosed AML (non-APL) participants who have lower EPBCR based on ≦1.5log on day 4 of the 3+7 regimen.
...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
83
Inclusion Criteria

  • Newly diagnosed AML, except for the APL subtype, according to the 2022 World Health Organization classification (WHO 2022 criteria)

  • Age ≥18 years and ≤70 years

  • Eligible for intensive chemotherapy

  • No prior chemotherapy for AML except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts>25x10^9/L)

  • Eastern Cooperative Oncology Group (ECOG) performance status≤2

  • Adequate renal function is defined as:

    • Serum creatinine≤2.0×upper limit of normal (ULN)
    • Creatinine clearance (CrCl)>30 mL/min calculated by the Cockcroft-Gault equation.

  • Adequate hepatic and heart function is defined as:

    • Serum total bilirubin≤1.5×ULN unless considered due to Gilbert's disease, or leukemic involvement
    • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)≤2.5×ULN, unless considered due to leukemic involvement
    • Myocardial enzyme<2.0×ULN
    • Left ventricular ejection fraction is within the normal range by measure of echocardiogram (ECHO)

  • Signed a written informed consent form (ICF)

  • Female participants who are of non-reproductive potential (i.e., post-menopausal by history of no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female participants of childbearing potential must have a negative serum pregnancy test upon study entry

Read More
Exclusion Criteria

  • AML with BCR-ABL1 or myeloid blast crisis of CML

  • Participants who have received prior treatment for AML with chemotherapy, hypomethylating agents, or venetoclax

  • Participants who are ineligible for intensive induction chemotherapy:

    • ≧71 years old OR

    • ≧18 to 70 years old and fulfill at least one criterion associated with lack of fitness for intensive induction chemotherapy:

      • ECOG PS of 2-3
      • Cardiac history of CHF requiring treatment or Ejection Fraction ≦50% or chronic stable angina
      • Diffusing capacity of the lungs for carbon monoxide (DLCO)≦65% or the forced expiratory volume in one second (FEVI) ≦65%

  • Participants with a prior history of MDS, MPN, or MDS/MPN

  • Participants with other concurrent malignant tumors on treatment, except for:

    • Malignancy treated with curative intent and with no known active disease present for ≧3 years
    • Adequately treated non-melanoma skin cancer or lentigo maligna without current evidence of disease
    • Adequately treated carcinoma in situ without current evidence of disease
    • Localized prostate cancer with a Gleason score of 6 or less

  • Pregnant or lactating women

  • Active heart disease is defined as any one of the following:

    • Uncontrolled or symptomatic angina pectoris
    • A myocardial infarction six months before enrolled
    • Arrhythmia needs medication or with severe clinical symptoms
    • Uncontrolled or symptomatic congestive heart failure (New York Hear Association [NYHA] classification> grade 2)

  • Participants with an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment

  • Participants with an active viral infection caused by HIV, hepatitis B, or hepatitis C virus that cannot be controlled by treatment

  • Participants with evidence of central nervous system leukemia before the study treatment

  • Participants with epilepsy which needs drug treatment, dementia, or other abnormal mental states that prevent understanding or following the protocol

  • Conditions that restrict the intake or absorption of orally administered drugs

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Assigned interventionsIdarubincinParticipants with EPBCR\>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy.
Assigned interventionsCytarabineParticipants with EPBCR\>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy.
Assigned interventionsVenetoclaxParticipants with EPBCR\>1.5 log (EPBCRhigh) complete the 3+7 regimen and are managed according to standard clinical practice. Participants with EPBCR≦1.5 log (EPBCRlow) receive intensified treatment with venetoclax orally along with the standard 3+7 regimen on days 5-14. A venetoclax dose ramp-up schedule is required in the first induction therapy.
Primary Outcome Measures
NameTimeMethod
CRc rate after one cycle of induction therapyUp to one month

The proportion of participants achieving CR/CRi by the initiation of next cycle of therapy (each cycle is 28 days).

Secondary Outcome Measures
NameTimeMethod
CRMRD-RateUp to 2 months

The cumulative proportion of participants achieving CR/CRi without measurable residual disease after two cycles of induction therapy and before starting the next cycle of therapy.

CRc rate after two cycle of induction therapyUp to 2 months

The cumulative proportion of participants achieving CR/CRi after two cycles of induction therapy and before starting the next cycle of therapy.

Event-free survival (EFS)Up to 12 months

The time from enrollment to treatment failure is defined as failure to achieve CR, CRi, or PR after two cycles of induction therapy, death from any cause, or relapse after achieving CR/CRi, whichever occurs first. If no specified events occur at the date of the last disease assessment, participants will be censored.

Relapse free survival (RFS)Up to 24 months

From the date of achieving CR/CRi until the date of documented relapse or death due to any cause or the last follow-up day. If no specified events occur at the date of the last disease assessment, participants will be censored.

Overall survival Overall survival (OS)Up to 24 months

The time from enrollment to death due to any cause. If death does not occur at the date of the last disease assessment, participants will be censored.

Trial Locations

Locations (1)

Affiliated hospital of Nantong University

🇨🇳

Nantong, Jiangsu, China

© Copyright 2024. All Rights Reserved by MedPath
HomeTerms & ConditionsPrivacy Policy