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

NCT06643962 | Recruiting

• 1 other identifier: TF-IIT-2024-01
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

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 Induction therapy (3+7 regimen).

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Keywords

acute myeloid leukemia; venetoclax; intensive chemotherapy; early peripheral blast clearance; newly diagnosed

Outcome Measures

Primary Outcomes (1)

• CRc rate after one cycle of induction therapy

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

  Up to one month

Secondary Outcomes (5)

• CRc rate after two cycle of induction therapy

  Up to 2 months

• CRMRD-Rate

  Up to 2 months

• Event-free survival (EFS)

  Up to 12 months

• Relapse free survival (RFS)

  Up to 24 months

• Overall survival Overall survival (OS)

  Up to 24 months

Other Outcomes (2)

• Baseline genomics

  Up to one month

• Baseline transcriptomics

  Up to one month

Study Arms (1)

Assigned interventions

EXPERIMENTAL

Participants 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.

Drug: Venetoclax; Drug: Idarubincin; Drug: Cytarabine

Interventions

Venetoclax DRUG

Venetoclax in the EPBCRlow cohort will be added to the ongoing 3+7 regimen. In the first induction cycle: venetoclax needs to be ramped up: 100 mg on day 5, 200mg on day 6, and 400mg on days 7-14, orally once daily. In the second induction (if required), venetoclax 400mg will be administered orally once daily on days 5-14 without a dose ramp-up schedule. Venetoclax in the EPBCRlow cohort during consolidation therapy: 400mg on days 1-7, orally once daily, along with the consolidation chemotherapy.

Also known as: Bcl-2 inhibitors

Assigned interventions

Idarubincin DRUG

Idarubicin (IDA): 10mg/m\^2/d (age \<60 years old) or 6mg/m\^2/d on days 1-3, intravenously (IV).

Also known as: IDA

Assigned interventions

Cytarabine DRUG

During induction therapy: 100mg/m2/d on days 1-7, IV. During consolidation therapy: intermediate-dose cytarabine for age \>55 years old: 1.0g/m\^2 q12h on days 1-3, high-dose cytarabine for age ≦55 years old: 2g/m2 q12h on days 1-3.

Also known as: Ara-C

Assigned interventions

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Affiliated Hospital of Nantong University: lead

Study Sites (1)

Affiliated hospital of Nantong University

Nantong, Jiangsu, 226001, China

RECRUITING

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Interventions

venetoclax; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Yingxin Sun, Dr

CONTACT

+86-13646249970; syx20194132088@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 16, 2024
• Study Start: October 31, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): October 31, 2027
• Last Updated: November 12, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)