Clinical trial NCT05603884: VCA Regimen Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Official title: Venetoclax Combining Chidamide and Azacitidine (VCA) Regimen Followed by Dicitabine Combined With Liposome Mitoxantrone, Cytarabine, and G-CSF (D-MAG) Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) : A Multicenter, Prospective, Single Arm Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Leukemia, Myeloid, Acute
AML Stage, Adult
Keywords: newly diagnosed acute myeloid leukemia
liposome mitoxantrone
sequential treatment
Lead sponsor: The First Affiliated Hospital of Xiamen University
Sponsor class: OTHER
Collaborators: name: Chipscreen Biosciences, Ltd.
name: CSPC Pharmaceutical Group Limited
name: Fujian Provincial Hospital
name: Fujian Cancer Hospital
name: Zhangzhou manicipal hospital of Fujian Province
name: Jieyang People's Hospital
name: Huizhou Municipal Central Hospital
First posted: 2022-11-03
Enrollment: 66
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Detailed description: Elderly Patients with AML have inferior outcomes due to poor physical condition, and intolerant to conventional chemotherapy. The regimen of Venetoclax and Azacitidine has been widely used in these patients and has proved to achieve higher CR rate than low intensity therapy. However, the median duration of response (DOR) of this regimen is about one year. Chidamide is a histone deacetylase (HDAC) inhibitor and preclinical data showed adding low-dose Chidamide to venetoclax could significantly promoted apoptosis of leukemia cell lines. The Venetoclax Combining Chidamide and Azacitidine (VCA) regimen was applied to one 62-year-old male patient with AML who achieved CR. Meanwhile, Liposome mitoxantrone has better safety and tolerance than mitoxantrone in elderly patients. Thus, this study is intended to use 2 cycles of VCA regimens followed by 2 cycles of D-MAG regimens, and then repeat the above four courses of treatment once to improve the median event free survival of elderly AML patients.

Eligibility criteria: Inclusion Criteria:

* 1) Histologically confirmed acute myeloid leukemia (non-M3). Treatment-na?ve and unable to receive standard cytarabine and anthracycline induction regimens due to age or comorbidities or patient preference.

  2) Age ≥ 60 years old, male or female, with an expected survival more than 3 months.

  3) Estimated creatinine clearance ≥ 30 mL/min. 4) AST and ALT ≤ 3.0 x ULN (unless leukemic organ involvement). Bilirubin ≤ 1.5 x ULN (unless considered due to leukemic organ involvement).

  5) ECOG ≤ 2. 6) Able to understand and voluntarily provide informed consent.

Exclusion Criteria:

* 1)Acute promyelocytic leukemia (APL) and low risk cytogenetics such as t(8;21), inv(16) or t(16;16).

  2) Active central nervous system leukemia. 3) History of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR- ABL1 translocation.

  4) HIV positive patients and/or HBV or HCV active infection (documented by HBV-DNA and HCV-RNA positive test) 5) Patients suffering from chronic respiratory diseases that require continuous oxygen inhalation, or a history of obvious renal, nervous system, psychiatric, endocrine, metabolic, immune, liver, and cardiovascular diseases 6) Patients suffering from malabsorption syndrome or other conditions that exclude enteral route of administration.

  7) Patients has clinically significant QTc prolongation (\>450 ms in men; \>470 ms in women), ventricular tachycardia and atrial fibrillation, second-degree heart block, myocardial infarction within the year prior to enrollment, and congestive heart failure;and patients with coronary heart disease with clinical symptoms requiring drug treatment.

  8) Active, uncontrolled severe infection. 9) History of other malignancies within 2 years, except for the following: Adequately treated cervix or breast cancer in situ; Basal cell cancer or local squamous cell carcinoma of the skin; 10) White blood cell count \> 25 × 10\^9/L. (Hydroxyurea or leukapheresis may meet this criterion.) 11) Mental disorders that hinder research participation 12) Participants have received the following treatments: hypomethylating agents, veneclax and/or chemotherapy for myelodysplastic syndrome (MDS), solid organ transplantation.

  13) Any other circumstances that the investigator believes that the patient is not suitable to participate in this trial

Primary outcomes:
measure: Complete remission (CR) rate
timeFrame: 6 months
Secondary outcomes:
measure: 1 year leukemia free survival (LFS)
timeFrame: 1 year from treatment initiation
measure: 1 year overall survival (OS)
timeFrame: 1 year from treatment initiation
measure: Adverse events
timeFrame: 6 months
measure: objective response rate (ORR)
timeFrame: 6 months
Other outcomes:
Locations:
city: Xiamen
country: China
facility: Bing Xu
state: Fujian
Study officials:
affiliation: The First Affiliated Hospital of Xiamen University
name: Bing Xu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: