A Study on the Efficacy and Safety of Venetoclax Combined With HAA Regimen in Newly Diagnosed Young AML.

Acute Myeloid Leukemia Clinical Trial

Official title:

The Second Affiliated Hospital of Kunming Medical University

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05893472
• Other study ID #: SHEN-PJ-KE-2023-125
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 1, 2023
• Est. completion date: April 1, 2024

Study information

• Verified date: May 2023
• Source: The Second Affiliated Hospital of Kunming Medical University
• Contact: ZePing Zhou, Dr
• Phone: 18788571605
• Email: zhouzeping[@]kmmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the efficacy and safety of the combination of venetoclax and HAA regimen in young, newly diagnosed acute myeloid leukemia patients under the age of 60.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 60 Years

Eligibility

Inclusion Criteria:

• The eligible subjects for enrollment in this study must meet all of the following

criteria:

1. Patients with acute myeloid leukemia (excluding APL) who meet the diagnostic criteria of the World Health Organization (WHO) 2016 classification.

2. Patients with AML and multilineage dysplasia (MDS) and/or myeloproliferative neoplasms (MPN) who meet the WHO criteria without prior history of MDS or MPN.

3. Patients with AML who are not classified separately according to the WHO classification, except for those with acute megakaryoblastic leukemia with bone marrow fibrosis or myeloid sarcoma.

4. Age greater than 16 years and less than 60 years, regardless of gender.

5. Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2.

6. Requirements for laboratory parameters (within 7 days prior to treatment initiation) include: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =3 times the upper limit of normal (ULN); serum bilirubin =2×ULN; serum cardiac enzyme <2.0×ULN; serum creatinine =2.0×ULN; and echocardiogram (ECHO)-determined ejection fraction within the normal range.

7. A signed informed consent form is required before any study-specific procedures are performed. Patients 18 years and older may sign the informed consent form themselves or have it signed by their next of kin. Patients under 18 years of age must have the informed consent form signed by their legal guardian. In consideration of the patient's medical condition, if it is not in the patient's best interest to sign the form, the legal guardian or patient's next of kin may sign the form on the patient's behalf.

Exclusion Criteria:

• Subjects meeting any of the following criteria will be excluded from this study:

1. Previously treated patients (including those who have undergone induction chemotherapy regardless of treatment response).

2. Secondary leukemia (including therapy-related AML subtype according to the World Health Organization (WHO) classification and those with a history of MDS and/or MPD).

3. Concomitant hematologic diseases (such as hemophilia or myelofibrosis) deemed unsuitable for inclusion by the investigator; individuals with prior abnormal blood counts are allowed to participate if they have been previously excluded from MDS and MPD.

4. Other malignant tumors requiring treatment.

5. Pregnant or lactating women. Female participants of childbearing potential must have a negative pregnancy test within 7 days prior to the start of the trial. Male or female participants must take contraceptive measures during the trial and for 3 years after completion of treatment.

6. Significant abnormalities in liver or kidney function beyond the inclusion criteria.

7. Active heart disease, defined as one or more of the following:

1. History of uncontrolled or symptomatic angina pectoris;

2. Myocardial infarction within 6 months prior to enrollment;

3. History of arrhythmia requiring medication or with severe clinical symptoms;

4. Uncontrolled or symptomatic congestive heart failure (> NYHA class 2);

5. Ejection fraction below the lower limit of the normal range. 8. Severe infectious diseases (e.g., unhealed tuberculosis or pulmonary aspergillosis).

9. Participants deemed unsuitable for inclusion by the investigator.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Venetoclax

Intervention

Combination Product:
• combination of venetoclax and HAA regimen
Using the combination of venetoclax and HAA regimen as induction therapy in young, newly diagnosed adult acute myeloid leukemia patients under the age of 60.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Kunming Medical University.	Kunming	Yunnan

Sponsors (7)

Lead Sponsor	Collaborator
ZePing Zhou	Guizhou Provincial People's Hospital, Handan Central Hospital, Second Xiangya Hospital of Central South University, Taian City Central Hospital, Tianjin People's Hospital, Western War Zone General Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Jin J, Wang JX, Chen FF, Wu DP, Hu J, Zhou JF, Hu JD, Wang JM, Li JY, Huang XJ, Ma J, Ji CY, Xu XP, Yu K, Ren HY, Zhou YH, Tong Y, Lou YJ, Ni WM, Tong HY, Wang HF, Mi YC, Du X, Chen BA, Shen Y, Chen Z, Chen SJ. Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2013 Jun;14(7):599-608. doi: 10.1016/S1470-2045(13)70152-9. Epub 2013 May 9. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Minimal residual disease (MRD)	MRD percentage	up to 12 months
Secondary	overall survival (OS)	Overall Survival (OS) is used to evaluate all patients enrolled in a clinical trial, from the date of enrollment until death from any cause or the date of last follow-up for surviving patients.	up to 12 months
Secondary	relapse-free survival (RFS)	Relapse-Free Survival (RFS) is only used to evaluate patients who achieve complete remission (CR) through reinduction therapy. RFS is defined as the time from achievement of CR until death from any cause, relapse, or the date of last follow-up.	up to 12 months
Secondary	30-day mortality rate	The 30-day mortality rate is used to evaluate all patients enrolled in a clinical trial, and is defined as the percentage of patients who die within 30 days of starting chemotherapy.	Within 30 days after starting the medication
Secondary	adverse drug reactions	Adverse drug reactions during chemotherapy and follow-up	up to 12 months