Trial Title:
Mitoxantrone Hydrochloride Liposome Combined With Chemotherapy in Untreated de Novo Acute Myeloid Leukemia
NCT ID:
NCT05941585
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Venetoclax
Mitoxantrone
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Mitoxantrone hydrochloride liposome injection30mg/m2
Description:
Mitoxantrone hydrochloride liposome intravenous infusion on day 1 (30mg/m2)
Arm group label:
mitoxantrone hydrochloride liposome injection combined with cytarabine and venetoclax
Arm group label:
mitoxantrone hydrochloride liposome injection combined with of cytarabine
Intervention type:
Drug
Intervention name:
HomoharringtonineD1-D7(2mg/m2/day)
Description:
Homoharringtonine intravenous infusion on D1-D7,2mg/m2/day in a 4-week treatment cycle.
Arm group label:
mitoxantrone hydrochloride liposome with cytarabine and homoharringtonine
Intervention type:
Drug
Intervention name:
Venetoclax (d4 100mg/day, d5200mg/day ,d6-d12 400mg/day)
Description:
Venetoclax d4-d12 (d4 100mg/day, d5200mg/day ,d6-d12 400mg/day)in a 4-week treatment
cycle.
Arm group label:
mitoxantrone hydrochloride liposome injection combined with cytarabine and venetoclax
Intervention type:
Drug
Intervention name:
Cytarabine(standard-dose:d1-d7100mg/m2/day)
Description:
Cytarabine intravenous infusion on d1-d7 ,100mg/m2/day
Arm group label:
mitoxantrone hydrochloride liposome injection combined with cytarabine and venetoclax
Arm group label:
mitoxantrone hydrochloride liposome injection combined with of cytarabine
Intervention type:
Drug
Intervention name:
Cytarabine(intermediate-dose:d1-d4100mg/m2/day, d5-d7 1g/m2)
Description:
d1-d4100mg/m2/day, d5-d7 1g/m2
Arm group label:
mitoxantrone hydrochloride liposome with cytarabine and homoharringtonine
Intervention type:
Drug
Intervention name:
Mitoxantrone hydrochloride liposome injection24mg/m2
Description:
Mitoxantrone hydrochloride liposome intravenous infusion on day 1 (24mg/m2)
Arm group label:
mitoxantrone hydrochloride liposome with cytarabine and homoharringtonine
Summary:
The purpose of this study is to determine the safety, efficacy and pharmacokinetics of
mitoxantrone hydrochloride liposome injection combined with chemotherapy in previously
untreated de novo acute myeloid leukemia.
Detailed description:
This is a prospective, multi-center, randomized, open-label, three-arm clinical study to
explore the efficacy among three chemotherapy regimens combined with mitoxantrone
hydrochloride liposome in previously untreated de novo acute myeloid leukemia. Patients
will be randomized to different treatment group and be given different induction therapy
in the first cycle. If patients do not achieve Morphologic Leukemia-free State (MLFS)
after the first induction cycle, they will receive the second induction therapy with
mitoxantrone hydrochloride liposome, cytarabine and venetoclax. Mitoxantrone
hydrochloride liposome will be given on day 1 at the dose of 24 mg/m2 or 30 mg/m2 and be
combined with cytarabine, venetoclax or homoharringtonine. A maximum of 2 cycles of
induction therapy are planned.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Able to understand the study and voluntarily sign informed consent.
2. Age: 18~65 (including 18) years old, gender unlimited.
3. Patients diagnosed with acute myeloid leukemia according to "The 2016 revision to
the World Health Organization classification of myeloid neoplasms and acute
leukemia" who haven't been treated.
4. Eastern Cooperative Oncology Group (ECOG) physical state score: 0-1.
5. Fit for intensive chemotherapy.
6. The function of main organs should meet the following standards before treatment:
Kidney: Serum creatinine ≤ 1.5 × Upper limit of normal range (ULN) Liver: Total
bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 3× ULN
7. Patients should agree to use contraception (such as intrauterine device [IUD],
contraceptive pill or condom) during the study period and within 6 months after the
end of the study; Female patients must have a negative serum pregnancy test within 7
days before enrollment.
Exclusion Criteria:
1. Any of the following cases:(1) diagnosed as acute promyelocytic leukemia (APL);(2)
chronic myelogenous leukemia in blast crisis;(3) AML with central nervous system
leukemia.
2. AML arising from prior cytotoxic chemotherapy or radiotherapy for other tumours.
3. Patient has been previously diagnosed with another malignancy in last 5 years
(except for cured basal cell carcinoma of skin or cervical carcinoma in situ).
4. Has been previously treated with doxorubicin or other anthracyclines and drugs for
AML.
5. Allergic history of mitoxantrone hydrochloride injection or any other drugs used in
this study.
6. Those on systemic anti-infective therapy with poorly controlled infection (signs of
infection progression within 1 week prior to the first dose, or as determined by the
investigator).
7. Patient who is suffering from severe hemorrhagic diseases, such as haemophilia A,
haemophilia B, von Willebrand disease and any other spontaneous bleeding require
medical treatment.
8. The estimated survival time is less than 3 months.
9. Any of the following conditions occurs in cardiac function:(1) Long QTc syndrome or
QTc interval > 480 ms;(2) Complete left bundle branch block or severe
atrioventricular block disease (without a pacemaker);(3) Serious and uncontrolled
arrhythmias and unstable angina pectoris requiring drug treatment;(4) History of
chronic congestive heart failure, New York Heart Association (NYHA)≥grade 3;(5) The
cardiac ejection fraction is less than 50% in Echocardiography;(6)Uncontrollable
hypertension (defined as multiple measurements of systolic blood pressure > 150 mmHg
or diastolic blood pressure > 90 mmHg under drug control);(7) History of myocardial
infarction, unstable angina pectoris, viral myocarditis or severe pericardial
disease, ECG evidence of acute ischemia or active conduction system abnormalities
within 6 months before first dose.
10. Patients have thromboembolic events within 6 months prior to first dose, such as
cerebrovascular accidents (including transient ischemic attack) and pulmonary
embolism.
11. HBsAg/HBcAb positive with HBV-DNA higher than the lower limit of the detection value
of the research center , hepatitis C antibody-positive with HCV-RNA higher than the
lower limit of the detection value of the research center, or HIV antibody positive
in the preliminary screening.
12. Patients who have been treated with strong/moderate CYP3A inducers/inhibitors or
P-gp inhibitors within 7 days prior to first dose (for treatment group 3 only).
13. Patients who cannot take oral medications or have absorption disorder (for treatment
group 3 only).
14. Patient is suffering from any serious and /or non-controllable disease, or the
investigator determines that the disease might affect the participation of patients
in the study, including (but not limited to, uncontrolled diabetes, dialysis related
kidney diseases, severe liver diseases, life-threatening autoimmune diseases and
hemorrhagic diseases, drug abuse, neurological diseases, etc.).
15. Pregnant or lactating female.
16. Patients who are not suitable for this study as decided by the investigator due to
other reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology & Blood Diseases Hospital
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Jianxiang Wang, Dr.
Phone:
86-22-23909120
Email:
wangjx@medmail.com.cn
Investigator:
Last name:
Jianxiang Wang, Dr.
Email:
Principal Investigator
Start date:
August 8, 2023
Completion date:
December 2026
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05941585
