Relapsed or Refractory Acute Myeloid LeukemiaPhase 1/2NCT05522192
Clinical Study of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia
A Phase 1/2 study testing Mitoxantrone liposome and Venetoclax in people with Relapsed or Refractory Acute Myeloid Leukemia, run by Hui Zeng at 1 site in China.
Trial summary
This study is an open-label, single-arm, phase I/II clinical study. Phase I is a multi-center, dose-escalation study, aiming to explore the maximum tolerated dose (MTD) of venetoclax combined with mitoxantrone liposome in the treatment of relapsed or refractory acute myeloid leukemia (AML), and determine the… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Relapsed or Refractory Acute Myeloid Leukemia
- What is being tested?
- Mitoxantrone liposome and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteChina
- Study dates
- 21 Jul 2022to May 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Jinan University
Guangzhou, Guangdong, 510632
Hui Zeng, MD
About this study
Official title: Clinical Study of Venetoclax Combined With Mitoxantrone Liposome in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
This study is an open-label, single-arm, phase I/II clinical study. Phase I is a multi-center, dose-escalation study, aiming to explore the maximum tolerated dose (MTD) of venetoclax combined with mitoxantrone liposome in the treatment of relapsed or refractory acute myeloid leukemia (AML), and determine the recommended dose for phase II (RP2D); Phase II is a multi-center, exploratory study, aiming to explore efficacy of venetoclax combined with mitoxantrone liposome in the treatment of relapsed and refractory AML patients, and to explore the differences in the efficacy of this combination therapy with different gene mutations.
Read the 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).
- Being tested
- Mitoxantrone liposome, Venetoclax
- Keywords
- venetoclax; Mitoxantrone liposomes; Acute myeloid leukemia
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitoxantrone liposomeDrug
Also called Mitoxantrone Hydrochloride Liposome Injection
Phase I: 24mg/m2, 30 mg/m2, 36mg/m2, IV, d1; Phase II: RP2D.
VenetoclaxDrug
Also called Venclexta
Phase I/II: 100mg po d1，200mg po d2，400mg po d3-28.
| Study group | Role | What they receive |
|---|---|---|
| Venetoclax-Mitoxantrone liposome | Experimental | Phase I
Mitoxantrone liposome
* Level 1: 24mg/m^2, ivgtt, d1;
* Level 2: 30mg/m^2, ivgtt, d1;
* Level 3: 36mg/m^2, ivgtt, d1;
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. Receives: Drug: Mitoxantrone liposome; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: MTD of mitoxantrone liposomes
To evaluate the tolerability of mitoxantrone liposomes combination regime
Measured: At the end of Cycle 1 (each cycle is 28 days)
Phase II: Composite complete remission rate (CRc)
To evaluate the efficacy of anti-leukemia
Measured: At the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes (9)
Phase I: Composite complete remission rate (CRc)
To evaluate the efficacy of anti-leukemia
Measured: At the end of Cycle 2 (each cycle is 28 days)
Phase I: Objective response rate (ORR)
To evaluate the efficacy of anti-leukemia
Measured: At the end of Cycle 2 (each cycle is 28 days)
Phase I: Relapse free survival (RFS)
To evaluate the efficacy of anti-leukemia
Measured: Up to 2 years
Phase I: Overall survival (OS)
To evaluate the efficacy of anti-leukemia
Measured: Up to 2 years
Phase I: Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)
To identify the incidence of AE and SAE in clinical trial
Measured: From the initiation of the first dose to 28 days after the last dose
Phase II: Objective response rate (ORR)
To evaluate the efficacy of anti-leukemia
Measured: At the end of Cycle 2 (each cycle is 28 days)
Phase II: Relapse free survival (RFS)
To evaluate the efficacy of anti-leukemia
Measured: Up to 4 years
Phase II: Overall survival (OS)
To evaluate the efficacy of anti-leukemia
Measured: Up to 4 years
Phase II: Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)
To identify the incidence of AE and SAE in clinical trial
Measured: From the initiation of the first dose to 28 days after the last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2022
- Study start21 Jul 2022
- Primary completionNov 2025 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hui Zeng
- Sponsor type
- University, hospital or other
- Collaborators
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor-investigator, Hui Zeng, First Affiliated Hospital of Jinan University
- Investigators
- Hui Zeng, M.D, Principal investigator, First Affiliated Hospital of Jinan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05522192
- Sponsor's protocol ID
- CSPC-DED-AML-K04
- Status last verified
- Aug 2022
- First submitted
- 12 Aug 2022
- Last updated
- 30 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of Venetoclax Combined With Mitoxantrone Liposome in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05522192
- Acronym / sponsor ID
- CSPC-DED-AML-K04
- Keywords
- venetoclax; Mitoxantrone liposomes; Acute myeloid leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Hui ZengUniversity, hospital or other
- Collaborators
- CSPC Ouyi Pharmaceutical Co., Ltd.
- Study start
- 21 Jul 2022 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 30 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, single-arm, phase I/II clinical study. Phase I is a multi-center, dose-escalation study, aiming to explore the maximum tolerated dose (MTD) of venetoclax combined with mitoxantrone liposome in the treatment of relapsed or refractory acute myeloid leukemia (AML), and determine the recommended dose for phase II (RP2D); Phase II is a multi-center, exploratory study, aiming to explore efficacy of venetoclax combined with mitoxantrone liposome in the treatment of relapsed and refractory AML patients, and to explore the differences in the efficacy of this combination therapy with different gene mutations.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Venetoclax-Mitoxantrone liposome | Experimental | Drug: Mitoxantrone liposome, Drug: VenetoclaxPhase I Mitoxantrone liposome * Level 1: 24mg/m^2, ivgtt, d1; * Level 2: 30mg/m^2, ivgtt, d1; * Level 3: 36mg/m^2, ivgtt, d1; 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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);
Key exclusion criteria (11 listed)
- 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.);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitoxantrone liposomeAlso: Mitoxantrone Hydrochloride Liposome InjectionPhase I: 24mg/m2, 30 mg/m2, 36mg/m2, IV, d1; Phase II: RP2D. | Drug | Venetoclax-Mitoxantrone liposome |
| VenetoclaxAlso: VenclextaPhase I/II: 100mg po d1，200mg po d2，400mg po d3-28. | Drug | Venetoclax-Mitoxantrone liposome |
Primary outcome
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
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
9 secondary outcomes
Phase I: Composite complete remission rate (CRc)
Time frame: 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)
Phase I: Relapse free survival (RFS)
Time frame: Up to 2 years
Phase I: Overall survival (OS)
Time frame: 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
Phase II: Objective response rate (ORR)
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Phase II: Relapse free survival (RFS)
Time frame: Up to 4 years
Phase II: Overall survival (OS)
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hui Zeng, M.D principal investigator
First Affiliated Hospital of Jinan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mitoxantrone liposome and Venetoclax in people with Relapsed or Refractory Acute Myeloid Leukemia, run by Hui Zeng at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hui Zeng, M.D (+86-18002201919, xyzengh@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: MTD of mitoxantrone liposomes (time frame: At the end of Cycle 1 (each cycle is 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2022.