Trial Title:
A Prospective, Multicenter, and Exploratory Study of CMGV in the Treatment of Recurrent Adult AML and MDS-EB-2/Elder AML
NCT ID:
NCT06329999
Condition:
Recurrent Adult Acute Myeloid Leukemia
Myelodysplastic Syndrome
Adult Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Recurrence
Conditions: Keywords:
Mitoxantrone Hydrochloride Liposomes
Cytarabine
Venetoclax
Recurrent Adult Acute Myeloid Leukemia
MDS-EB-2
Adult Acute Myeloid Leukemia
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CMGV
Description:
Initial treatment induction therapy: CMG+Vineclavone regimen Mitoxantrone liposomes
15mg/m2, iv, d1; Cytarabine 10mg/m2, H, q12h, d1-7; G-CSF starts at 5ug/kg, H, d0, WBC ≥
30 × 109/L, stop G-CSF; Vinecla 100mg, 2200mg, 3400mg, d4-10. Every 4 weeks is a cycle,
for a total of 2 cycles. For patients with CR/CRI/MLFS/PR in the first cycle, repeat this
regimen for consolidation treatment once (the second course of treatment is Vineclavone
400mg d1-7).
Follow up treatment: Patients who meet the transplantation criteria will undergo
hematopoietic stem cell transplantation, while those who do not undergo transplantation
will continue to receive CMG+Vineclavone consolidation for 4-6 courses.
Arm group label:
CMGV regime
Other name:
CMGV REGIME
Summary:
The goal of this clinical trial] is to evaluate mitoxantrone hydrochloride liposomes,
subcutaneous injection of cytarabine and G-CSF combined with Venetoclax (CMG+Ven) in
adult secondary acute myeloid leukemia and myelodysplastic syndrome with increased
primordial cells type 2(MDS-IB2) or elderly acute myeloid leukemia]. The main questions
it aims to answer are:
- Evaluation of the efficacy
- Evaluation of the safety
Detailed description:
Mitoxantrone is a traditional anthracycline drug. It exerts anti-tumor effects by
interfering with DNA, RNA and inhibiting topoisomerase II. It is a cell cycle
non-specific drug ; Mitoxantrone has been used in AML patients. It is widely used in both
induction and relapse and refractory treatment stages . At the same time, the literature
shows that there is no complete cross-resistance between mitoxantrone and other
anthracycline drugs, and it is still effective for patients who have relapsed after
previous first-line anthracycline treatment . In addition, the CMG (standard dose
cytarabine + mitoxantrone + G-CSF) prestimulation regimen has many applications in China
; a study showed that 16 cases of elderly AML (50% were early in the elderly The CR rate
of the CMG regimen for the treatment of secondary AML was 50%, the ORR was 87.4%, and the
median OS was 12 months in 2006; a study applied the CMG regimen vs. the conventional
dose MA regimen (mitoxantrone + arabinoside Glucoside) in the treatment of elderly AML,
the results showed that there was no significant difference in efficacy between the two
regimens, but the CMG group had a shorter bone marrow suppression period and less
bleeding and infection than the MA group in 2014. Since there is no drug for mitoxantrone
in the domestic market for a long period of time, its clinical application is limited.
Mitoxantrone Hydrochloride Liposomal Injection is a Class 2 new drug independently
developed by CSPC. It will be launched in China in 2022. The approved indications are:
those who have received at least first-line standard treatment (including chemotherapy,
autologous hematopoietic stem cell transplantation, etc.) For patients with relapsed or
refractory peripheral T-cell lymphoma (PTCL), the registration key phase II clinical
trial showed good therapeutic effects in relapsed or refractory PTCL and NKTCL, with a
confirmed ORR of 41.7%; among them, NKTCL subtype The type has remarkable efficacy,
breaking through the limitations of NKTCL's natural resistance to anthracyclines in
previous clinical experience. The ORR of single-drug treatment can reach 42.9%.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The patient fully understands this study, voluntarily participates and signs an
informed consent form (ICF);
- Age: 18-75 years old (including boundary values of 18 and 75);
- Clinically confirmed adult AML and MDS-IB2 (WHO 2022 standard) patients, AML
patients meet any of the following criteria:
1. Treatment related AML
2. Previously had a history of MDS
3. Associated with MDS related genes/chromosomal abnormalities
4. Previously had a history of CMML
5. Age ≥ 60 years old
6. Previous history of prodromal MPN, including ET, PV, and MF, with bone marrow
fibrosis ≤ grade 2 (according to the 0-3 grade standard)；
- For elderly AML or MDS patients, the comprehensive evaluation should be based on the
Fit population: ECOG<3, no major comorbidities, and MMSE and SPPB meet the standards
(refer to Appendix 8-11);
- Expected survival time ≥ 3 months;
- Liver and kidney function: alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) ≤ 3 times the upper limit of normal value (ULN) (≤ 5 times
the upper limit of normal value for patients with liver infiltration); Total
bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of
normal value for patients with liver infiltration); Serum creatinine ≤ 1.5 times the
upper limit of normal value;
- The relevant treatment for MDS (excluding blood transfusion) must be completed 2
weeks before the start of the study treatment; In the case of rapidly proliferative
diseases, hydroxyurea is allowed to be used until 24 hours before the start of the
study treatment. Before starting the research treatment,Toxicity related to previous
MDS treatment must be restored to level 2 or below.
Exclusion Criteria:
The researchers determined that patients who are not suitable to participate in this
study. If a patient meets any of the following criteria, they will not be allowed to
enter this study:
- The subject's previous history of anti-tumor treatment meets one of the following
conditions:
1. Individuals who have previously received mitoxantrone or mitoxantrone
liposomes;
2. Previously received treatment with doxorubicin or other anthracyclines, with a
total cumulative dose of doxorubicin>360mg/m2 (1mg of doxorubicin is equivalent
to 2mg of doxorubicin or 0.5mg of doxorubicin);
3. Within 4 weeks prior to the first use of the study drug or within 5 half-lives
of the drug, the patient has received anti-tumor treatment including surgery,
chemotherapy, targeted therapy, or participated in other clinical trials and
received clinical trial medication;
- Heart function and disease meet one of the following conditions:
1. Long QTc syndrome or QTc interval>480ms;
2. Complete left bundle branch block, II or III degree atrioventricular block;
3. Severe and uncontrolled arrhythmias that require medication treatment;
4. The New York College of Cardiology in the United States has a classification of
≥ II;
5. Cardiac ejection fraction (LVEF) below 50%;
6. A history of myocardial infarction, unstable angina, severe unstable
ventricular arrhythmias, or any other arrhythmias requiring treatment, a
history of clinically severe pericardial disease, or evidence of acute ischemic
or active conduction system abnormalities on electrocardiogram within the 6
months prior to recruitment.
- Patients who have previously or currently suffered from other malignant tumors
(except for effectively controlled non melanoma skin basal cell carcinoma,
breast/cervical carcinoma in situ, and other malignant tumors that have not been
treated for more than 6 months and have been effectively controlled, as well as
patients who have received long-term non chemotherapy treatments such as hormone
therapy);
- Uncontrollable systemic diseases (such as infection during the promotion period,
uncontrollable hypertension, diabetes, etc.);
- Central nervous system leukemia;
- Secondary AML patients with bone marrow fibrosis ≥ grade 3;
- CML patients with sudden changes;
- Accompanied by a well prognosis chromosome karyotype t (8; 21) (q22; q22.1) RUNX1::
RUNX1T1, inv (16) (p13.1 q22) CBFB: MYH11, as well as acute promyelocytic leukemia;
- Human immunodeficiency virus (HIV) infected individuals (HIV antibody positive);
- Active infection of hepatitis B and hepatitis C (if hepatitis B B surface antigen or
core antibody is positive, HBV-DNA will be tested additionally, and if HBV-DNA
exceeds 1x103 copies/mL, it will be excluded; if hepatitis C antibody is positive,
HCV-RNA will be tested additionally, and if hepatitis C virus RNA exceeds 1x103
copies/mL, it will be excluded);
- Have a known history of immediate or delayed hypersensitivity reactions to similar
drugs and excipients in the study drug;
- Accompanied by a history of severe neurological or mental illness;
- The researchers determined that there were patients who were not suitable to
participate in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Ruijin Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
xiaoqian Xu, Doctor
Phone:
13816205940
Email:
Ellenxxq@qq.com
Start date:
February 3, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Ruijin Hospital
Agency class:
Other
Collaborator:
Agency:
Huadong Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Agency class:
Other
Collaborator:
Agency:
Huashan Hospital
Agency class:
Other
Collaborator:
Agency:
Army Medical Center of PLA
Agency class:
Other
Collaborator:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
RenJi Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai Jiading District Central Hospital
Agency class:
Other
Collaborator:
Agency:
The Second Affiliated Hospital of Dalian Medical University
Agency class:
Other
Collaborator:
Agency:
First Hospital of China Medical University
Agency class:
Other
Collaborator:
Agency:
Dalian Municipal Central Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai Pudong Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai Public Health Clinical Center
Agency class:
Other
Collaborator:
Agency:
Xuhui Central Hospital, Shanghai
Agency class:
Other
Collaborator:
Agency:
The Affiliated People's Hospital of Ningbo University
Agency class:
Other
Collaborator:
Agency:
Taizhou First People's Hospital
Agency class:
Other
Collaborator:
Agency:
Wenzhou People's Hospital
Agency class:
Other
Source:
Ruijin Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06329999
