- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05522192
Clinical Study of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia
Clinical Study of Venetoclax Combined With Mitoxantrone Liposome in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Study Overview
Status
Intervention / Treatment
Detailed Description
This study is an open-label, single-arm, phase I/II clinical study. Phase I is a multi-center, dose-escalation study. Following the "3+3" principle, it plans to recruit 9-18 patients with clinically diagnosed relapsed or refractory AML who will be treated with venetoclax and mitoxantrone liposome, in order to explore the MTD of mitoxantrone liposome, and determine the RP2D. Mitoxantrone liposome began to explore the dose from 24 mg/m^2, and every 4 weeks (28 days) was a cycle. Three dose groups of 24, 30 and 36 mg/m^2 were preseted; The trial phase includes screening period (within 28 days), treatment period (planned 2 cycles), follow-up period (RFS and OS follow-up, planned 1 year).
Phase II is a multi-center, exploratory study, aiming to explore efficacy of venetoclax combined with mitoxantrone liposome in the treatment of relapsed or refractory AML patients, and to explore the differences in the efficacy of this combination therapy with different gene mutations. After Phase I reaches MTD and the dose of Phase II is determined, Phase II clinical trials will be carried out. The phase II trial phase includes screening period (within 28 days) , treatment period (planned 6 cycles ) and a follow-up period (RFS and OS follow-up, planned for 1 year).
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Hui Zeng, M.D
- Phone Number: +86-18002201919
- Email: xyzengh@hotmail.com
Study Contact Backup
- Name: Huien Zhan, M.M.
- Phone Number: +86-19926098944
- Email: zhanhuien@163.com
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510632
- Recruiting
- First Affiliated Hospital of Jinan University
-
Contact:
- Hui Zeng, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- AML confirmed by bone marrow cytology and pathology;
- Meet the diagnostic criteria for relapsed and refractory AML. Diagnostic criteria for relapsed AML: leukemia cells reappeared in peripheral blood after complete remission or blast cells in bone marrow >0.05 (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration. Diagnostic criteria for refractory AML: naive patients who were ineffective after 2 courses of standard regimens; patients who relapsed within 12 months after consolidation and intensive therapy after CR; patients who relapsed after 12 months but were ineffective after conventional chemotherapy; 2 or more Secondary relapse; persistent extramedullary leukemia;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
- Liver and kidney function: Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) (≤5 x ULN for patients with liver infiltrates); Total bilirubin ≤1.5 x ULN (≤3 x ULN for patients with liver infiltration); Serum creatinine ≤1.5 x ULN;
- Normal cardiac function: left ventricular ejection fraction (LVEF) ≥ 45% assessed by echocardiography or radionuclide active angiography (MUGA);
- Pulmonary function: dyspnea ≤ CTC AE grade 1 and SaO2 ≥ 92% in indoor air environment;
- The expected survival time is greater than 3 months;
- Patients voluntarily participated in this study and signed the informed consent.
Exclusion Criteria:
- The subject had previously received any of the following anti-tumor treatments: a)Those who have previously received mitoxantrone or mitoxantrone liposome; b)Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin is more than 360 mg/m^2 (1 mg doxorubicin converted from other anthracycline drugs is equivalent to 2 mg daunorubicin or 0.5 mg idarubicin); c)Have received anti-tumor treatment (including chemotherapy, targeted therapy, hormone therapy, taking traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the study drugs;
- Heart function and disease meet one of the following conditions: a)Long QTc syndrome or QTc interval > 480 ms; b)Complete left bundle branch block, grade II or III atrioventricular block; c)Serious and uncontrolled arrhythmias requiring drug treatment; d)New York Heart Association grade ≥ II; e)A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
- Identify patients with central nervous system invasion;
- Other malignancies, except for effectively controlled non melanoma skin basal cell carcinoma, breast / cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment in the past five years;
- Non controlled systemic diseases (such as active infection, non controlled hypertension, diabetes, etc.);
- Human immunodeficiency virus (HIV) infection (HIV antibody positive);
- Active hepatitis B and C infection (hepatitis B test: if there is a positive hepatitis B surface antigen or core antibody, add HBV DNA, and the hepatitis B virus DNA exceeds 1x10^3 copies/mL to exclude; hepatitis C: if the hepatitis C antibody is positive, further test HCV RNA, hepatitis C Viral RNA exceeding 1x10^3 copies/mL was excluded);
- Hypersensitivity to any study drug or its components;
- Pregnant women, lactating women, patients who refused to take effective contraceptive measures during the study;
- Serious neurological or psychiatric history;
- Unsuitable subjects for this study determined by the investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Venetoclax-Mitoxantrone liposome
Phase I Mitoxantrone liposome
Venetoclax: 100mg po d1, 200mg po d2, 400mg po d3-28. Every 4 weeks is a cycle, a total of 2 cycles, the first cycle to observe DLT. Phase II Mitoxantrone liposome: RP2D Venetoclax: 100mg po d1, 200mg po d2, 400mg po d3-28. 28 days is a cycle, and a maximum of 6 cycles can be carried out. If the patient achieves CR, CRi or PR, if the patient can tolerate it, it will be used for 6 cycles; if the patient is suitable for transplantation, it can also enter the transplantation path; If the patient was evaluated as NR (no response) after 2 cycles, he could withdraw from the study. |
Phase I: 24mg/m2, 30 mg/m2, 36mg/m2, IV, d1; Phase II: RP2D.
Other Names:
Phase I/II: 100mg po d1,200mg po d2,400mg po d3-28.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: MTD of mitoxantrone liposomes
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
To evaluate the tolerability of mitoxantrone liposomes combination regime
|
At the end of Cycle 1 (each cycle is 28 days)
|
Phase II: Composite complete remission rate (CRc)
Time Frame: At the end of Cycle 2 (each cycle is 28 days)
|
To evaluate the efficacy of anti-leukemia
|
At the end of Cycle 2 (each cycle is 28 days)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Composite complete remission rate (CRc)
Time Frame: At the end of Cycle 2 (each cycle is 28 days)
|
To evaluate the efficacy of anti-leukemia
|
At the end of Cycle 2 (each cycle is 28 days)
|
Phase I: Objective response rate (ORR)
Time Frame: At the end of Cycle 2 (each cycle is 28 days)
|
To evaluate the efficacy of anti-leukemia
|
At the end of Cycle 2 (each cycle is 28 days)
|
Phase I: Relapse free survival (RFS)
Time Frame: Up to 2 years
|
To evaluate the efficacy of anti-leukemia
|
Up to 2 years
|
Phase I: Overall survival (OS)
Time Frame: Up to 2 years
|
To evaluate the efficacy of anti-leukemia
|
Up to 2 years
|
Phase I: Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)
Time Frame: From the initiation of the first dose to 28 days after the last dose
|
To identify the incidence of AE and SAE in clinical trial
|
From the initiation of the first dose to 28 days after the last dose
|
Phase II: Objective response rate (ORR)
Time Frame: At the end of Cycle 2 (each cycle is 28 days)
|
To evaluate the efficacy of anti-leukemia
|
At the end of Cycle 2 (each cycle is 28 days)
|
Phase II: Relapse free survival (RFS)
Time Frame: Up to 4 years
|
To evaluate the efficacy of anti-leukemia
|
Up to 4 years
|
Phase II: Overall survival (OS)
Time Frame: Up to 4 years
|
To evaluate the efficacy of anti-leukemia
|
Up to 4 years
|
Phase II: Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)
Time Frame: From the initiation of the first dose to 28 days after the last dose
|
To identify the incidence of AE and SAE in clinical trial
|
From the initiation of the first dose to 28 days after the last dose
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Hui Zeng, M.D, First Affiliated Hospital of Jinan University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Antineoplastic Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Venetoclax
- Mitoxantrone
Other Study ID Numbers
- CSPC-DED-AML-K04
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Relapsed or Refractory Acute Myeloid Leukemia
-
Shanxi Bethune HospitalAntengene CorporationRecruitingRelapsed or Refractory Acute Myeloid LeukemiaChina
-
University Hospital, ToulouseRecruitingRelapsed or Refractory Acute Myeloid LeukemiaFrance
-
Seoul National University HospitalPharos iBio Co., Ltd.RecruitingRelapsed or Refractory Acute Myeloid LeukemiaKorea, Republic of
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.TerminatedRelapsed or Refractory Acute Myeloid Leukemia (AML)China
-
Aptose Biosciences Inc.RecruitingRelapsed or Refractory Acute Myeloid LeukemiaUnited States, Germany, Spain, Korea, Republic of, Australia, New Zealand
-
CStone PharmaceuticalsCompletedRelapsed or Refractory Acute Myeloid LeukemiaChina
-
University of PennsylvaniaTerminatedRelapsed or Refractory Acute Myeloid LeukemiaUnited States
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Not yet recruitingTreatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML)China
-
Tarapeutics Science Inc.RecruitingRelapsed or Refractory Acute Myeloid Leukemia (AML)China
-
AstraZenecaTerminatedRelapsed or Refractory Acute Myeloid Leukemia (AML)United States
Clinical Trials on Mitoxantrone liposome
-
Huijing WuBeijing Xisike Clinical Oncology Research Foundation; CSPC Pharmaceutical GroupRecruitingAngioimmunoblastic T-cell LymphomaChina
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Not yet recruitingPeripheral T Cell LymphomaChina
-
Second Affiliated Hospital of Soochow UniversityThe Affiliated Hospital of Xuzhou Medical UniversityRecruitingRelapsed/Refractory Multiple MyelomaChina
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.TerminatedAdvanced Gastric CarcinomaChina
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Suspended
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Unknown
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.CompletedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerChina
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.TerminatedA Study of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Relapsed Ovarian CancerPlatinum-resistant Ovarian CancerChina
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Active, not recruitingAdvanced Solid TumorChina
-
European Organisation for Research and Treatment...CompletedOvarian CancerFrance, Spain, United Kingdom, Belgium, Israel, Switzerland, Italy