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Intensive Therapy Combined With Venetoclax for Adult Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

with or without venetoclax

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring acute myeloid leukemia, adult, newly diagnosed, venetoclax, intensive chemotherapy

Eligibility Criteria

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

Inclusion Criteria:

Patients with newly diagnosed AML (except for APL subtype) according to 2016 World Health Organization (WHO) classification and have not received chemotherapy before.
Age ≥18 years and ≤65 years.
Patient considered eligible for intensive chemotherapy.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at randomization.
Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of norm (ULN) or creatinine clearance >40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR).
Adequate hepatic function as evidenced by:(1) Serum total bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's disease, or leukemic involvement following approval by the Coordinating Investigator or Trial Coordinator;(2) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN, unless considered due to leukemic involvement following approval by the Coordinating Investigator or Trial Coordinator;(3)Myocardial enzyme<2.0×upper limit normal;(4)Left ventricular ejection fraction are within the normal range by measure of echocardiogram (ECHO)
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 > 25x109/L).
Able to understand and willing to sign an informed consent form (ICF).

Exclusion Criteria:

AML with BCR-ABL1; or myeloid blast crisis of CML.
Subjects who have received a prior treatment for AML with chemotherapy , hypomethylating agents or venetoclax before.
Subjects with acute panmyelosis with myelofibrosis or myeloid sarcoma defined by WHO 2016.
Subjects with a prior history of MDS, MPN or MDS/MPN.
Subjects with other concurrent malignant tumors on treatment with the exception of basal or squamous cell carcinoma of the skin,carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding of prostate cancerand need treatment.
Pregnant or lactating women.
Active heart disease, defined as anyone of the followings:(1) Uncontrolled or symptomatic angina pectoris;(2) A myocardial infarction 6 months before enrolled; (3)Arrhythmia needed medication or with severe clinical symptoms;(4)Uncontrolled or symptomatic congestive heart failure (NYHA> grade 2);(5)Left ventricular ejection fraction below the lower limit of the normal range.
Subjects with an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
Subjects with an active viral infection caused by HIV, hepatitis B or hepatitis C virus that cannot be controlled by treatment.
Subjects with evidence of central nervous system leukemia before treatment.
Subjects with epilepsy which needs drug treatment, dementia, or other abnormal mental state that can't understand or follow the protocol.
Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Venetoclax combined with intensive chemotherapy

Intensive chemotherapy only

Arm Description

The experimental group receives two cycles of inducation chemotherapy consisting of venetoclax combined with standard DA 3+7 regimen. After CR/CRi achieved, subjects proceed allo-transplantation or consolidation therapy according to their ELN risks. The consolidation chemotherapy regimen consists of three cycles of intermediate （for age>55 years）or high（for age≤ 55 years） dose cytarabine combined with venetoclax.

The control group receives two cycles of inducation chemotherapy consisting of standard DA 3+7 regimen without venetoclax. After CR/CRi achieved, subjects proceed allo-transplantation or consolidation therapy according to their ELN risks. The consolidation chemotherapy regimen consists of three cycles of intermediate （for age>55 years）or high（for age≤ 55 years） dose cytarabine without venetoclax.

Outcomes

Primary Outcome Measures

Event-free survival

The time from randomization to treatment failure, death from any cause or relapse after achieving CR or CRi, whichever occurs first.

Secondary Outcome Measures

Overall survival Overall survival

The time from randomization to death resulting from any cause

CR rate

The proportion of patients achieving CR after two cycles of induction chemotherapy.

Rates of remission (CR/CRi) without measurable residual disease (CRMRD-)

The proportion of AML patients achieving CR/CRi with negativity for a genetic marker by real-time quantitative polymerase chain reaction and/or with negativity by multi-color flow cytometry.

Relapse free survival

From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day.

Cumulative incidence of relapse

Calculated from tdate of first CR to the date of relapse, considering nonrelapse mortality (NRM) as a competing event

Frequency and severity of AEs

Adverse clinical events in the course of drug treatment according to CTCAE v5.0.

Full Information

NCT ID

NCT05356169

First Posted

April 19, 2022

Last Updated

April 29, 2022

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

1. Study Identification

Unique Protocol Identification Number

NCT05356169

Brief Title

Intensive Therapy Combined With Venetoclax for Adult Acute Myeloid Leukemia

Official Title

A Phase 2/3 Prospective, Randomized, Controlled, Parallel Group Study of Intensive Therapy Combined With Venetoclax for Newly Diagnosed Adult Acute Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

June 2022 (Anticipated)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

June 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

300 patients will be randomly distributed into the control group (n=150) and the experimental group(n=150). Patients will receive two cycles of induction chemotherapy. The control group receives standard 3+7 induction regimen containing cytarabine (100mg/m2 d1-7) and daunorubicin (60mg/m2 d1-3). The experimental group receives venetoclax combined with intensive chemotherapy (3+7 induction regimen same as the control group). For each group, patients who fail to achieve CR/CRi after two courses of induction therapy may receive alternative therapy decided by their physicians. After CR/CRi achieved, subjects proceed allo-transplantation or consolidation therapy according to their ELN risks: subjects in favorable risk group should continue with chemotherapy; subjects in poor risk group should go through transplantation; for subjects in intermediate risk group, those with suitable donors can receive transplantation while others can continue with consolidation therapy. Subjects receive 3 courses of intermediate-dose cytarabine (1.5g/m2 q12h d1, 3, 5) for age>55 years or high dose cytarabine (3g/m2 q12h d1, 3, 5) for age≤ 55 years as consolidation therapy with venetoclax in experimental group and without venetoclax in control group. After consolidation, patients will be observed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia, adult, newly diagnosed, venetoclax, intensive chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Venetoclax combined with intensive chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Intensive chemotherapy only

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

with or without venetoclax

Intervention Description

Bcl-2 inhibitor

Primary Outcome Measure Information:

Title

Event-free survival

Description

The time from randomization to treatment failure, death from any cause or relapse after achieving CR or CRi, whichever occurs first.

Time Frame

up to 12 months

Secondary Outcome Measure Information:

Title

Overall survival Overall survival

Description

The time from randomization to death resulting from any cause

Time Frame

up to 36 months

Title

CR rate

Description

The proportion of patients achieving CR after two cycles of induction chemotherapy.

Time Frame

up to 2 months

Title

Rates of remission (CR/CRi) without measurable residual disease (CRMRD-)

Description

The proportion of AML patients achieving CR/CRi with negativity for a genetic marker by real-time quantitative polymerase chain reaction and/or with negativity by multi-color flow cytometry.

Time Frame

up to 2 months

Title

Relapse free survival

Description

From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day.

Time Frame

up to 36 months

Title

Cumulative incidence of relapse

Description

Calculated from tdate of first CR to the date of relapse, considering nonrelapse mortality (NRM) as a competing event

Time Frame

up to 36 months

Title

Frequency and severity of AEs

Description

Adverse clinical events in the course of drug treatment according to CTCAE v5.0.

Time Frame

up to 8 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with newly diagnosed AML (except for APL subtype) according to 2016 World Health Organization (WHO) classification and have not received chemotherapy before. Age ≥18 years and ≤65 years. Patient considered eligible for intensive chemotherapy. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at randomization. Adequate renal function as evidenced by serum creatinine ≤ 2.0 × upper limit of norm (ULN) or creatinine clearance >40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR). Adequate hepatic function as evidenced by:(1) Serum total bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's disease, or leukemic involvement following approval by the Coordinating Investigator or Trial Coordinator;(2) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 2.5 × ULN, unless considered due to leukemic involvement following approval by the Coordinating Investigator or Trial Coordinator;(3)Myocardial enzyme<2.0×upper limit normal;(4)Left ventricular ejection fraction are within the normal range by measure of echocardiogram (ECHO) 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 > 25x109/L). Able to understand and willing to sign an informed consent form (ICF). Exclusion Criteria: AML with BCR-ABL1; or myeloid blast crisis of CML. Subjects who have received a prior treatment for AML with chemotherapy , hypomethylating agents or venetoclax before. Subjects with acute panmyelosis with myelofibrosis or myeloid sarcoma defined by WHO 2016. Subjects with a prior history of MDS, MPN or MDS/MPN. Subjects with other concurrent malignant tumors on treatment with the exception of basal or squamous cell carcinoma of the skin,carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding of prostate cancerand need treatment. Pregnant or lactating women. Active heart disease, defined as anyone of the followings:(1) Uncontrolled or symptomatic angina pectoris;(2) A myocardial infarction 6 months before enrolled; (3)Arrhythmia needed medication or with severe clinical symptoms;(4)Uncontrolled or symptomatic congestive heart failure (NYHA> grade 2);(5)Left ventricular ejection fraction below the lower limit of the normal range. Subjects with an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment Subjects with an active viral infection caused by HIV, hepatitis B or hepatitis C virus that cannot be controlled by treatment. Subjects with evidence of central nervous system leukemia before treatment. Subjects with epilepsy which needs drug treatment, dementia, or other abnormal mental state that can't understand or follow the protocol. Conditions that limit the ingestion or gastrointestinal absorption of orally administered drugs.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jianxiang Wang, Dr

Phone

86-22-23909120

wangjx@medmail.com.cn

12. IPD Sharing Statement

Learn more about this trial

Intensive Therapy Combined With Venetoclax for Adult Acute Myeloid Leukemia

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