Venetoclax + Decitabine vs. "7+3" Induction Chemotherapy in Young AML

Sponsor
Chen Suning (Other)
Overall Status
Recruiting
CT.gov ID
NCT05177731
Collaborator
(none)
188
Enrollment
1
Location
2
Arms
34
Anticipated Duration (Months)
5.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research is being done to assess the therapeutic efficacy and safety of a promising (venetoclax and decitabine) versus conventional "7+3"chemotherapy in induction young patients with acute myeloid leukemia.

This study involves the following:

Venetoclax and decitabine (investigational combination) Cytarabine and idarubicin (per standard of care)

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

This is an open-label, multicenter, phase Ⅲ randomized clinical trial to compare the therapeutic efficacy and safety of conventional induction chemotherapy (7+3 regimen) to the combination of venetoclax and decitabine among fit, young adults with newly diagnosed acute myeloid leukemia (AML).

Conventional induction chemotherapy with idarubicin and cytarabine is the standard of induction chemotherapy for acute myeloid leukemia (AML).

The FDA has approved the combination therapy of venetoclax and decitabine for elderly (> 60 year old) patients with newly diagnosed AML not eligible for intensive chemotherapy. Venetoclax is an inhibitor of BCL-2 (B-cell lymphoma 2, a protein that initiates tumor growth, disease progression, and drug resistance), which can lead to cancer cell death. Decitabine, a demethylation agent, has the potential to synergically target leukemia stem cell populations when combined with venetoclax as its homologous drug azacytidine.

Participants will be randomly assigned to one of the different induction groups and followed with either consolidated chemotherapy or allogeneic hematopoietic stem cell transplantation after remission. After completion of study treatment, participants are followed up every 3 to 6 months for up to 2 years.

It is expected that about 188 people will take part in this research study.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
188 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
De novo adult AML patients randomly assigned to two induction treatment groups: venetoclax+decitabine group and conventional idarubicin(12mg/m2)+cytarabine group.De novo adult AML patients randomly assigned to two induction treatment groups: venetoclax+decitabine group and conventional idarubicin(12mg/m2)+cytarabine group.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Comparing the Efficacy and Safety of Venetoclax Combined With Decitabine Versus Conventional "7+3" Induction Chemotherapy of Acute Myeloid Leukemia in Young Adults
Actual Study Start Date :
Mar 1, 2022
Anticipated Primary Completion Date :
Oct 31, 2023
Anticipated Study Completion Date :
Dec 31, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: Investigational ( venetoclax, decitabine)

Randomized participants will receive induction as decitabine on days 1-5 and venetoclax daily on days 1-28. Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%):Re-induction with pre-induction therapy. Consolidation: If patients with favorable risk and MRD (Minimal Residual Disease) negative or refuse to allo-HSCT (Hematopoietic stem-cell transplantation), high dose cytarabine (2g/m3 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, high dose cytarabine for 1-2 cycles and follow up with allo-HSCT.

Drug: Venetoclax
Orally by mouth
Other Names:
  • Venclexta
  • Drug: Decitabine for Injection
    Intravenous infusion

    Experimental: Standard of Care (Conventional Induction "7+3")

    Randomized participants will receive cytarabine and idarubicin per standard of care as follows: Induction: cytarabine on days 1-7 and idarubicin (12mg/m2) on days 1-3 . Second Induction (if not reach complete remission, but the percentage of blaste cells in bone marrow decreased by more than 50%): Re-induction with pre-induction therapy. Consolidation: If patients with favorable risk and MRD negative or refuse to allo-HSCT, high dose cytarabine (2g/m3 q12h days 1-3) for 4 cycles. If patients with intermediate or poor risk or favorable risk but MRD positive, high dose cytarabine for 1-2 cycles and follow up with allo-HSCT.

    Drug: Cytarabine
    Intravenous infusion
    Other Names:
  • Ara-C
  • Drug: Idarubicin
    Intravenous infusion
    Other Names:
  • IDA
  • Outcome Measures

    Primary Outcome Measures

    1. Overall response rate (ORR) [From randomization to 2 cycles of induction before consolidation therapy(100 days)]

      Complete remission/complete remission with incomplete count recovery/Morphologic Leukemia Free State

    Secondary Outcome Measures

    1. Incidence of severe infection (>=grade 3 ) [From randomization to 2 cycles of induction before consolidation therapy(100 days)]

      Assessed using CTCAE 5

    2. Duration of myelosuppression [From randomization to 2 cycles of induction before consolidation therapy(100 days)]

      The duration of absolute value of peripheral blood neutrophils <0.5×10^9/L and platelet count <50×10^9/L during myelosuppression.

    3. Event free survival [From the time from randomization to time for up to 2 years]

      Events include progressive disease, relapse, changes in treatment regimens, fatal or intolerable side effects and any death.

    4. Overall survival [From the time from randomization to time for up to 2 years]

      Overall survival

    5. Rate of Minimal Residual Disease (MRD) negativity [From randomization to 2 cycles of induction before consolidation therapy(100 days)]

      Percentage of participants who converted to MRD < 10^-3 before initiation of consolidation therapy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 59 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male or female, 59 > =Age (years) >= 18;

    2. Newly diagnosed as AML patients according to World Health Organization (WHO) classification;

    3. Patients have not received prior therapy for AML (except hydroxyurea and Ara-C<1.0g/d);

    4. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1, 2 ;

    5. Liver function: Total bilirubin ≦3 upper limit of normal (ULN); aspartate aminotransferase (AST) ≦3 ULN; alanine aminotransferase (ALT)≦3 ULN(except extramedullary infiltration of leukemia)

    6. Renal function:Ccr(Creatinine Clearance Rate) ≧30 ml/min;

    7. Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.

    Exclusion Criteria:
    1. Acute promyeloid leukemia;

    2. AML with central nervous system (CNS) infiltration;

    3. Patients have received prior hypomethylating agents (HMA) therapy for myelodysplastic syndrome (MDS) and progressed to AML;

    4. HIV infection;

    5. Patients with severe heart failure (grade 3-4) ;

    6. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a) Uncontrolled and/or active systemic infection (viral, bacterial or fungal); b) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment.

    1. An active second cancer that requires treatment within 6 months of study entry
    1. Patients deemed unsuitable for enrolment by the investigator;

    2. Patients willing to receive intensive induction chemotherapy

    3. Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen;

    4. Patients reject to participate in the study.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1The First Affiliated Hospital of Soochow University, Jiangsu Institute of HematologySuzhouJiangsuChina215000

    Sponsors and Collaborators

    • Chen Suning

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chen Suning, Physician, The First Affiliated Hospital of Soochow University
    ClinicalTrials.gov Identifier:
    NCT05177731
    Other Study ID Numbers:
    • SZ-AML02
    First Posted:
    Jan 5, 2022
    Last Update Posted:
    Mar 15, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Chen Suning, Physician, The First Affiliated Hospital of Soochow University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 15, 2022