Safety and Efficacy of Venetoclax in Combination With Azacitidine and HA Regimen in the Treatment of AML in the Elderly

NCT05949762 | Unknown Phase 1

• 1 other identifier: SHEN-PJ-KE-2023-157
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective phase II, single-arm clinical study that plans to enroll 45 patients aged 60 years or older with primary AML diagnosed after April 1, 2023.The purpose of this trial is to evaluate the efficacy of Venetoclax in combination with azacitidine and HA regimens in elderly patients aged \>60 years with primary acute myeloid leukemia and to provide evidence for optimal selection of clinical treatment regimens.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  which evaluates the efficacy of patient induction therapy, including complete remission (CR), complete remission with incomplete blood count recovery (CRi), and morphologic leukemia-free state (MLFS)

  up to 12 months

Secondary Outcomes (5)

• Minimal residual disease (MRD)

  up to 12 months

• overall survival (OS)

  up to 12 months

• relapse-free survival (RFS)

  up to 12 months

• 30-day mortality rate

  Within 30 days after starting the medication

• adverse drug reactions

  up to 12 months

Study Arms (1)

Venetoclax in Combination With Azacitidine and HA Regimen

EXPERIMENTAL

Details for: Venetoclax 200mg d1-10 Azacitidine 100mg/d (or 50-75mg/m2/d), d2-7 Hautriacontin 2mg/m2/d, d3-7 Cytarabine 100mg/m2/d, d3-8 (infusion 24h)

Procedure: Venetoclax in Combination With Azacitidine and HA Regimen

Interventions

Venetoclax in Combination With Azacitidine and HA Regimen PROCEDURE

Patients diagnosed with primary AML based on morphology, immunophenotyping, and history and meeting the inclusion exclusion criteria were induced with Venetoclax in combination with Azacitidine and HA regimen. Details for: Venetoclax 200mg d1-10 Azacitidine 100mg/d (or 50-75mg/m2/d), d2-7 Hautriacontin 2mg/m2/d, d3-7 Cytarabine 100mg/m2/d, d3-8 (infusion 24h)

Venetoclax in Combination With Azacitidine and HA Regimen

Eligibility Criteria

• Age: 60 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with acute myeloid leukemia other than APL who meet the World Health Organization diagnostic criteria (WHO 2016 criteria);
• those with AML not otherwise classified under the World Health Organization AML classification except for acute myeloproliferative disorder with myelofibrosis and myeloid sarcoma.
• Age \> 60 years, male or female.
• Have a score of 0-2 on the Eastern Cooperative Oncology Group Physical Status Scale (ECOG-PS).
• pass the requirements of the following laboratory test indicators (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; serum cardiac enzymes \< 2.0 x ULN; serum creatinine ≤ 2.0 x ULN; 2) Cardiac ejection fraction within normal values as determined by cardiac ultrasound (ECHO).
• Informed consent had to be signed before all specific study procedures were started, and the informed consent was signed by the patient himself/herself or his/her immediate family members; in view of the patient's condition, if the signature of the patient himself/herself was not conducive to the treatment of his/her condition, the informed consent was signed by his/her legal guardian or the patient's immediate family members.

You may not qualify if:

• 、Treated patients (is defined as having received induction chemotherapy in the past, regardless of the efficacy).
• , Concurrent malignant tumors of other organs (those requiring treatment). 3, Patients participating in the trial must use contraception during the trial treatment and within 3 years after completion of treatment.
• , Significantly abnormal liver and kidney function beyond the enrollment criteria.
• \. Active heart disease, defined as one or more of the following:
• History of uncontrolled or symptomatic angina;
• Myocardial infarction less than 6 months from study entry;
• A history of arrhythmia requiring medication or clinically significant symptoms;
• Uncontrolled or symptomatic congestive heart failure (\> NYHA class 2);
• Ejection fraction below the lower limit of the normal range. 6. severe infectious diseases (untreated tuberculosis, pulmonary aspergillosis).
• \) Those deemed unsuitable for enrollment by the investigator

Sponsors & Collaborators

• ZePing Zhou: lead
• Handan Central Hospital: collaborator
• Taian City Central Hospital: collaborator
• Tianjin People's Hospital: collaborator
• Guizhou Provincial People's Hospital: collaborator
• Second Xiangya Hospital of Central South University: collaborator
• Western War Zone General Hospital: collaborator

Study Sites (1)

The Second Affiliated Hospital of Kunming Medical University.

Kunming, Yunnan, China

RECRUITING

Related Publications (8)

• Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015 Sep 17;373(12):1136-52. doi: 10.1056/NEJMra1406184. No abstract available.

  PMID: 26376137 BACKGROUND

• 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

• DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Dohner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hajek R, Porkka K, Illes A, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971.

  PMID: 32786187 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

• DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, Kadia TM, Borthakur G, Ohanian M, Alvarado Y, Issa GC, Montalban-Bravo G, Short NJ, Yilmaz M, Bose P, Jabbour EJ, Takahashi K, Burger JA, Garcia-Manero G, Jain N, Kornblau SM, Thompson PA, Estrov Z, Masarova L, Sasaki K, Verstovsek S, Ferrajoli A, Weirda WG, Wang SA, Konoplev S, Chen Z, Pierce SA, Ning J, Qiao W, Ravandi F, Andreeff M, Welch JS, Kantarjian HM, Konopleva MY. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020 Oct;7(10):e724-e736. doi: 10.1016/S2352-3026(20)30210-6. Epub 2020 Sep 5.

  PMID: 32896301 BACKGROUND

• DiNardo CD, Lachowiez CA, Takahashi K, Loghavi S, Xiao L, Kadia T, Daver N, Adeoti M, Short NJ, Sasaki K, Wang S, Borthakur G, Issa G, Maiti A, Alvarado Y, Pemmaraju N, Montalban Bravo G, Masarova L, Yilmaz M, Jain N, Andreeff M, Jabbour E, Garcia-Manero G, Kornblau S, Ravandi F, Konopleva MY, Kantarjian HM. Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia. J Clin Oncol. 2021 Sep 1;39(25):2768-2778. doi: 10.1200/JCO.20.03736. Epub 2021 May 27.

  PMID: 34043428 BACKGROUND

• Wei H, Wang Y, Gale RP, Lin D, Zhou C, Liu B, Qiu S, Gu R, Li Y, Zhao X, Wei S, Gong B, Liu K, Gong X, Liu Y, Zhang G, Song Z, Wang Y, Li W, Mi Y, Wang J. Randomized Trial of Intermediate-dose Cytarabine in Induction and Consolidation Therapy in Adults with Acute Myeloid Leukemia. Clin Cancer Res. 2020 Jul 1;26(13):3154-3161. doi: 10.1158/1078-0432.CCR-19-3433. Epub 2020 Feb 6.

  PMID: 32029439 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• ZePing Zhou

  The Second Affiliated Hospital of Kunming Medical University

  STUDY CHAIR

Central Study Contacts

yaxian tan

CONTACT

18208821198; 353964619@qq.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: July 18, 2023
• Study Start: April 1, 2023
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: July 18, 2023

Record last verified: 2023-07

Locations

CN (1)