Safety and Efficacy of Venetoclax Combination With Decitabine(DEC3-VEN) in the Treatment of AML in the Adult

NCT06285136 | Not Yet Recruiting Phase 2

• 1 other identifier: SHEN-PJ-KE-2024-15
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study proposes to conduct a prospective, multicenter, single-arm study to explore the efficacy and safety of venetoclax in combination with high-dose decitabine (DEC3-VEN) in new diagnosed adult patients with AML, and to provide evidence for the optimal selection of clinical treatment regimens, which is planned to be conducted in 10 research centers across the country.

Conditions

Acute Myeloid Leukemia, Adult

Outcome Measures

Primary Outcomes (1)

• ORR

  ORR (include CR, CRi, MLFS, PR) of the first course of Venetoclax in combination with high-dose decitabine for the treatment of newly-diagnosed AML adult patients.

  up to 24 months

Secondary Outcomes (1)

• Overall survival (OS)

  up to 24 months

Study Arms (1)

Venetoclax in combination with Decitabine (+-sorafenib)

EXPERIMENTAL

Venetoclax in combination with decitabine (+-sorafenib) Venetoclax (VEN) 100mg d1, 200mg d2, 400mg d3-14 Decitabine (DEC) 20mg/m2/q8h, d4-6 (infusion time \>2h) Sorafenib 800mg/d, d8-14 (only for FLT3/ITD mutation positive patients)

Procedure: DEC3-VEN

Interventions

DEC3-VEN PROCEDURE

Venetoclax in combination with decitabine (+-sorafenib) Venetoclax (VEN) 100mg d1, 200mg d2, 400mg d3-14 Decitabine (DEC) 20mg/m2/q8h, d4-6 (infusion time \>2h) Sorafenib 800mg/d, d8-14 (only for FLT3/ITD mutation positive patients)

Venetoclax in combination with Decitabine (+-sorafenib)

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects suitable for enrollment in this study must meet all of the following criteria:
• meet the World Health Organization diagnostic criteria (WHO2022 criteria) other than APL or carrying one of the abnormal karyotypes such as t(8;21)/(RUNX1::RUNX1TI), inv(16)(p13.1q22), t(16;16) (p13.1q22), t(16;16)/CBFβ::myh11), etc. Patients with acute myeloid leukemia other than those with one of the abnormal karyotypes such as t(16;16)/CBFβ::myh11
• Patients with AML not otherwise classified under the World Health Organization AML classification, except for acute myeloproliferative disorder with myelofibrosis and myeloid sarcoma;
• patients of either sex, age greater than or equal to 16 years and less than 65 years, with a primary diagnosis of AML, who are considered suitable for intensive chemotherapy;
• Eastern Cooperative Oncology Group (ECOG) physical status ≤ 2 at enrollment;
• the patient has not received prior treatment for AML (except hydroxyurea and Ara-C \<1.0 g/d for tumor composite reduction);
• passes the following laboratory test markers (performed within 7 days prior to treatment):1) aspartate aminotransferase (ALT), alanine aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN), serum bilirubin ≤ 2 x ULN; and serum cardiac enzymes \< 2.0 x ULN; unless leukemic organ involvement is considered.2) Creatinine ≥ 30 mL/min, calculated by the Cockcroft Gault formula or measured by 24-hour urine collection
• Female subjects of childbearing potential must have a negative pregnancy test result within 72 hours prior to the start of treatment; no pregnancy is planned during the study and within 6 months of the last dose of study drug, and a negative urine or serum pregnancy test result at screening. Men must use latex condoms during any sexual contact with WOCBP, even if they have undergone a successful vasectomy, and must agree to avoid childbearing (during treatment and within 6 months of the last dose of study drug);
• have a life expectancy of more than 2 months;
• informed consent must be signed prior to the start of all specific study procedures, either by the patient himself/herself or by a member of his/her immediate family; if, in view of the patient's medical condition, his/her own signature would not be conducive to the treatment of his/her medical condition, the informed consent will be signed by his/her legal guardian or by a member of the patient's immediate family.

You may not qualify if:

• Subjects may not be enrolled in this study if they meet any of the following criteria:
• AML with BCR-ABL1; or CML acute stage;
• Treatment-naïve patients (is defined as having received prior induction chemotherapy regardless of efficacy);
• Subjects with acute total myelopathy with myelofibrosis or myeloid sarcoma as defined by WHO 2016;
• Secondary leukemia (primarily those whose World Health Organization (WHO 2016) AML classification falls into the subcategory of treatment-related AML and those with a history of prior MDS and/or MPD);
• concurrent other hematologic diseases (e.g., hemophilia, myelofibrosis, etc., who are considered unsuitable for enrollment by the investigator; those who have previous blood abnormalities but have ever had bone marrow tests except for MDS and MPD are allowed to be enrolled);
• Pregnant or lactating patients;
• Those who are allergic to any drugs involved in this study;
• Have used strong or moderate CYP7A inducers within 3 days prior to the start of study treatment;
• concurrent malignant tumors of other organs (those requiring treatment);
• Significantly abnormal hepatic or renal function beyond the enrollment criteria;
• Active heart disease, defined as one or more of the following:1) Myocardial infarction less than 6 months from study entry; 2) A history of arrhythmia requiring medication or severe clinical symptoms; 3) Uncontrolled or symptomatic congestive heart failure (\> NYHA class 2); 4) Uncontrolled or symptomatic angina;5) Left ventricular ejection fraction below the lower limit of the normal range;
• severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis), patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C; subjects with uncontrolled treatment.
• Subjects with evidence of central nervous system leukemia prior to treatment;
• Subjects with epilepsy requiring medication, dementia, or other abnormal mental states that are unable to understand or follow the regimen;

Sponsors & Collaborators

• The Second Affiliated Hospital of Kunming Medical University: lead
• Chinese Academy of Medical Sciences: collaborator
• Handan Central Hospital: collaborator
• Taian City Central Hospital: collaborator
• Tianjin People's Hospital: collaborator
• Guizhou Provincial People's Hospital: collaborator
• Central South University: collaborator
• Western Theater General Hospital: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator
• Chengdu Jingdongfang Hospital: collaborator

Study Sites (1)

The Second Affiliated Hospital of Kunming Medical University.

Kunming, Yunnan, China

Location

Related Publications (5)

• Del Poeta G, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, Panetta P, Suppo G, Masi M, Amadori S. Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. 2003 Mar 15;101(6):2125-31. doi: 10.1182/blood-2002-06-1714. Epub 2002 Nov 7.

  PMID: 12424199 BACKGROUND

• Mei M, Aldoss I, Marcucci G, Pullarkat V. Hypomethylating agents in combination with venetoclax for acute myeloid leukemia: Update on clinical trial data and practical considerations for use. Am J Hematol. 2019 Mar;94(3):358-362. doi: 10.1002/ajh.25369. Epub 2018 Dec 13.

  PMID: 30499168 BACKGROUND

• Pettit K, Odenike O. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies. Front Oncol. 2015 Dec 14;5:280. doi: 10.3389/fonc.2015.00280. eCollection 2015.

  PMID: 26697412 BACKGROUND

• Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, Enjeti A, Tiong IS, Savona M, Lee S, Chyla B, Popovic R, Salem AH, Agarwal S, Xu T, Fakouhi KM, Humerickhouse R, Hong WJ, Hayslip J, Roboz GJ. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol. 2019 May 20;37(15):1277-1284. doi: 10.1200/JCO.18.01600. Epub 2019 Mar 20.

  PMID: 30892988 BACKGROUND

• Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Bernal del Castillo T, Al-Ali HK, Martinelli G, Falantes J, Noppeney R, Stone RM, Minden MD, McIntyre H, Songer S, Lucy LM, Beach CL, Dohner H. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015 Jul 16;126(3):291-9. doi: 10.1182/blood-2015-01-621664. Epub 2015 May 18.

  PMID: 25987659 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

ZePing Zhou

CONTACT

18788571605; zhouzeping@kmmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: February 18, 2024
• First Posted: February 29, 2024
• Study Start: March 1, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: February 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)