Treatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML)Phase 1/2NCT05100303
A Study to Evaluate the Tolerance and Efficacy of Mitoxantrone Hydrochloride Liposome Injection Combined With Cytarabine in Patients With Acute Myeloid Leukemia (AML)
A Phase 1/2 study testing Mitoxantrone Hydrochloride liposome injection and Cytarabine (LoDAC) in people with Treatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML), run by CSPC ZhongQi Pharmaceutical Technology Co., Ltd. at 1 site in China.
Trial summary
This is an open-label, multi-cohort, multi-center Phase Ib/II clinical study to evaluate the tolerance and efficacy of Mitoxantrone Hydrochloride liposome injection combined with cytarabine in patients with Acute Myeloid Leukemia (AML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML)
- What is being tested?
- Mitoxantrone Hydrochloride liposome injection and Cytarabine (LoDAC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteChina
- Study dates
- Dec 2021to Jun 2023
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients volunteer to participate in this study and sign the informed consent form.
- Age≥18 years old, no gender limitation.
- Patient has a diagnosis of newly diagnosed or relapsed or refractory(R/R) AML as determined by pathological and morphological results, according to World Health Organization (WHO) 2016 classification.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Patient must meet the following criteria as indicated on the clinical laboratory tests:a. Serum aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN);b. Serum total bilirubin ≤ 1.5 x ULN;c. Serum creatinine ≤ 1.5 x ULN.
- Patient and their partner agree to take effective contraception from the date of signing an informed consent to 180 days after the last dose; female patients must have negative urine or blood HCG (except for menopause and hysterectomy).
Who cannot join
- 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.
- 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).
- Patient is receiving continuous treatment for graft-versus-host disease (GVHD), or has received autologous or allogeneic stem cell transplantation more than once.
- Allergic history of mitoxantrone hydrochloride injection, cytarabine or liposome.
- Previously received doxorubicin or other anthracyclines, and the cumulative dose of doxorubicin exceeds 400 mg/m^2 (calculation of equivalent dose of anthracyclines: 1 mg doxorubicin = 2 mg epirubicin = 2 mg daunorubicin = 0.5 mg noroxydaunorubicin = 0.45 mg mitoxantrone; except doxorubicin liposomes).
- Patient has received any anti-tumor treatment within 2 weeks before the first dose (or within 5 half-lives of the drug), including chemotherapy, immunotherapy, targeted therapy, endocrine therapy and radiation therapy (local radiation therapy interval < 2 weeks). Leukopenia treatment (hydroxyurea, leukocyte separation, etc.) and preventive intrathecal injection exceeds 24 hours are the exception.
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- The non-hematological toxicity of previous anti-tumor treatment does not return to grade≤1 (except for alopecia, skin pigmentation or tolerable events judged by the investigator).
- Patient is receiving systemic anti-infection treatment but has poor response (there are signs of infection progression within 1 week prior to the first dose or determined by the investigator).
- The estimated survival time is less than 3 months.
- 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 (except for patients who use the 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% or lower than the lower limit of the laboratory test value range of the research center;(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 screening.
- Patients have thromboembolic events in the past 6 months, such as cerebrovascular accidents (including transient ischemic attack) and pulmonary embolism.
- HBsAg/HBcAb positive with HBV-DNA ≥2000 IU/mL, 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.
- Patients who have undergone major surgery (except intravenous infusion port implantation) within 3 months before the first study dose, or plan to perform major surgery during the study period.
- Patient is suffering from any serious and /or non-controllable disease, or the investigator determines that the disease might affect the participants 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.).
- Pregnant or lactating female.
- Patients are not suitable for the study in the investigator's opinion.
Trial locations and contacts
1 site in 1 country.
China1 site
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou
Jishi Wang, Chief doctor, +86-13639089646, Wangjishi9646@163.com
About this study
Official title: An Open-label, Multi-center Phase Ib/II Study to Evaluate the Tolerance and Efficacy of Mitoxantrone Hydrochloride Liposome Injection Combined With Cytarabine in Patients With Acute Myeloid Leukemia (AML)
This is an open-label, multi-cohort, multi-center Phase Ib/II clinical study to evaluate the tolerance and efficacy of Mitoxantrone Hydrochloride liposome injection combined with cytarabine in patients with Acute Myeloid Leukemia (AML). The study will be divided into two phases, the dose escalation phase and the dose expansion phase. Patients with relapsed or refractory(R/R) AML will be included in the dose-escalation phase, and patients with treatment-naïve or R/R AML will be included in the dose-expansion phase.
Read the detailed description
Dose escalation phase: Eligible patients will enter the screening period up to 14 days before the start of treatment. Patients will receive mitoxantrone liposomes combined with cytarabine, with a fixed dose of cytarabine and mitoxantrone liposomes in 3 dose groups: 24 mg/m^2, 30 mg/m^2 and 36 mg/m^2. The starting dose will be 24 mg/m^2, and the "3+3" principle is adopted for the escalation. If the maximum tolerated dose is not explored at the preset maximum dose (36 mg/m^2), the investigator and the sponsor will determine whether to continue the dose escalation, and it is necessary to ensure that 6 patients complete the dose-limiting toxicity (DLT) observation under this dose group. The treatment period includes 2 cycles with each cycle lasting 28 days. Cycle 1 is the DLT observation period and Cycle 2 is the extended dosing period. Mitoxantrone hydrochloride liposome injection will be given on the first day of each cycle, and cytarabine will be given every 12 hours on Day 1, 3, and 5 of each cycle. Patients who do not experience a DLT in the first cycle and achieve is at least PR, may enter the extended dosing period and be treated with the original regimen in Cycle 2. Patients who have completed 2 cycles and have a DLT in the first cycle or have not achieved PR will be withdrawn from treatment.
Dose expansion phase: Newly treated AML or R/R AML patients will be included and divided into two cohorts. Eligible patients will enter the screening period up to 14 days before receiving treatments. The treatment period is 2 cycles, and each cycle is 28 days. Mitoxantrone hydrochloride liposome injection will be given on the first day of each cycle, whose dose size will be determined by the investigator and the sponsor based on the results of the previous study. Cytarabine will be given on Day 1-7 of each cycle for the treatment-naïve group, and on Day 1, 3 and 5 of each cycle for the R/R group. Patients will take 1 cycle of therapy and will be assessed for response at the end of the 1st cycle. After the efficacy evaluation, the patient may receive a second cycle of chemotherapy at the investigator's discretion. And patients whose curative effect do not reach PR will be withdrawn from treatment.
- Being tested
- Mitoxantrone Hydrochloride liposome injection, Cytarabine (LoDAC)
- 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 Hydrochloride liposome injectionDrug
Mitoxantrone hydrochloride liposome will be administered by intravenous (IV) injections.
Cytarabine (LoDAC)Drug
Low-dose or high-dose cytarabine (LoDAC) will be administered by intravenous (IV) injections.
| Study group | Role | What they receive |
|---|---|---|
| Mitoxantrone Hydrochloride liposome and cytarabine | Experimental | Chemotherapy will be given in 28-day cycles, and total treatment period is 2 cycles.
Dose escalation phase:
Patients will receive 24 mg/m^2, 30 mg/m^2 or 36mg/m^2 of mitoxantrone hydrochloride liposome daily by intravenous (IV) injections on the first day and 1.5 g/m^2 of cytarabine twice daily by IV for 3 days (day 1, day3 and day5).
Dose expansion phase:
Patients with newly diagnosed AML will receive mitoxantrone hydrochloride liposome daily by IV on the first day, 100~200 mg/m^2 of cytarabine by IV for 7 days (day 1~7). Patients with R/R AML will receive mitoxantrone hydrochloride liposome daily by IV on the first day, 1.5 g/m^2 of cytarabine twice daily by IV for 3 days (day 1, day3 and day5). The dose size of mitoxantrone hydrochloride liposome will be determined by the investigator and the sponsor based on the results of the previous study. Receives: Drug: Mitoxantrone Hydrochloride liposome injection; Drug: Cytarabine (LoDAC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of dose-limiting toxicity (DLT)in dose escalation phase
Measured: The first cycle (28 days)
Adverse events during treatment in dose expansion phase
Measured: up to 3 years
Secondary outcomes (9)
Adverse events during treatment in dose escalation phase
Measured: up to 3 years
Composite CR rate (CRc: CR+CRi) in dose escalation phase
Measured: up to 3 years
Objective response rate (ORR) in dose escalation phase
Measured: up to 3 years
Overall survival (OS) in dose escalation phase
Measured: up to 3 years
Explore maximum tolerated dose (MTD) in dose escalation phase
Measured: up to 3 years
Composite CR rate (CRc: CR+CRi) in dose expansion phase
Measured: up to 3 years
Objective response rate (ORR) in dose expansion phase
Measured: up to 3 years
Overall survival (OS) in dose expansion phase
Measured: up to 3 years
Explore RP2D in dose expansion phase
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2021
- Study startDec 2021 (estimated)
- Primary completionNov 2022 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by CSPC ZhongQi Pharmaceutical Technology Co., Ltd.The sponsor's other registered studies.
- 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
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05100303
- Sponsor's protocol ID
- HE071-CSP-022
- Status last verified
- Oct 2021
- First submitted
- 19 Oct 2021
- Last updated
- 29 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center Phase Ib/II Study to Evaluate the Tolerance and Efficacy of Mitoxantrone Hydrochloride Liposome Injection Combined With Cytarabine in Patients With Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT05100303
- Acronym / sponsor ID
- HE071-CSP-022
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Dec 2021 (estimated)
- Primary completion
- Nov 2022 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 29 Oct 2021 (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 is an open-label, multi-cohort, multi-center Phase Ib/II clinical study to evaluate the tolerance and efficacy of Mitoxantrone Hydrochloride liposome injection combined with cytarabine in patients with Acute Myeloid Leukemia (AML). The study will be divided into two phases, the dose escalation phase and the dose expansion phase. Patients with relapsed or refractory(R/R) AML will be included in the dose-escalation phase, and patients with treatment-naïve or R/R AML will be included in the dose-expansion phase.
Detailed description
Dose escalation phase: Eligible patients will enter the screening period up to 14 days before the start of treatment. Patients will receive mitoxantrone liposomes combined with cytarabine, with a fixed dose of cytarabine and mitoxantrone liposomes in 3 dose groups: 24 mg/m^2, 30 mg/m^2 and 36 mg/m^2. The starting dose will be 24 mg/m^2, and the "3+3" principle is adopted for the escalation. If the maximum tolerated dose is not explored at the preset maximum dose (36 mg/m^2), the investigator and the sponsor will determine whether to continue the dose escalation, and it is necessary to ensure that 6 patients complete the dose-limiting toxicity (DLT) observation under this dose group. The treatment period includes 2 cycles with each cycle lasting 28 days. Cycle 1 is the DLT observation period and Cycle 2 is the extended dosing period. Mitoxantrone hydrochloride liposome injection will be given on the first day of each cycle, and cytarabine will be given every 12 hours on Day 1, 3, and 5 of each cycle. Patients who do not experience a DLT in the first cycle and achieve is at least PR, may enter the extended dosing period and be treated with the original regimen in Cycle 2. Patients who have completed 2 cycles and have a DLT in the first cycle or have not achieved PR will be withdrawn from treatment.
Dose expansion phase: Newly treated AML or R/R AML patients will be included and divided into two cohorts. Eligible patients will enter the screening period up to 14 days before receiving treatments. The treatment period is 2 cycles, and each cycle is 28 days. Mitoxantrone hydrochloride liposome injection will be given on the first day of each cycle, whose dose size will be determined by the investigator and the sponsor based on the results of the previous study. Cytarabine will be given on Day 1-7 of each cycle for the treatment-naïve group, and on Day 1, 3 and 5 of each cycle for the R/R group. Patients will take 1 cycle of therapy and will be assessed for response at the end of the 1st cycle. After the efficacy evaluation, the patient may receive a second cycle of chemotherapy at the investigator's discretion. And patients whose curative effect do not reach PR will be withdrawn from treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mitoxantrone Hydrochloride liposome and cytarabine | Experimental | Drug: Mitoxantrone Hydrochloride liposome injection, Drug: Cytarabine (LoDAC)Chemotherapy will be given in 28-day cycles, and total treatment period is 2 cycles. Dose escalation phase: Patients will receive 24 mg/m^2, 30 mg/m^2 or 36mg/m^2 of mitoxantrone hydrochloride liposome daily by intravenous (IV) injections on the first day and 1.5 g/m^2 of cytarabine twice daily by IV for 3 days (day 1, day3 and day5). Dose expansion phase: Patients with newly diagnosed AML will receive mitoxantrone hydrochloride liposome daily by IV on the first day, 100~200 mg/m^2 of cytarabine by IV for 7 days (day 1~7). Patients with R/R AML will receive mitoxantrone hydrochloride liposome daily by IV on the first day, 1.5 g/m^2 of cytarabine twice daily by IV for 3 days (day 1, day3 and day5). The dose size of mitoxantrone hydrochloride liposome will be determined by the investigator and the sponsor based on the results of the previous study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients volunteer to participate in this study and sign the informed consent form.
- Age≥18 years old, no gender limitation.
- Patient has a diagnosis of newly diagnosed or relapsed or refractory(R/R) AML as determined by pathological and morphological results, according to World Health Organization (WHO) 2016 classification.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Patient must meet the following criteria as indicated on the clinical laboratory tests:a. Serum aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN);b. Serum total bilirubin ≤ 1.5 x ULN;c. Serum creatinine ≤ 1.5 x ULN.
Key exclusion criteria (16 listed)
- 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.
- 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).
- Patient is receiving continuous treatment for graft-versus-host disease (GVHD), or has received autologous or allogeneic stem cell transplantation more than once.
- Allergic history of mitoxantrone hydrochloride injection, cytarabine or liposome.
- Previously received doxorubicin or other anthracyclines, and the cumulative dose of doxorubicin exceeds 400 mg/m^2 (calculation of equivalent dose of anthracyclines: 1 mg doxorubicin = 2 mg epirubicin = 2 mg daunorubicin = 0.5 mg noroxydaunorubicin = 0.45 mg mitoxantrone; except doxorubicin liposomes).
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 Hydrochloride liposome injectionMitoxantrone hydrochloride liposome will be administered by intravenous (IV) injections. | Drug | Mitoxantrone Hydrochloride liposome and cytarabine |
| Cytarabine (LoDAC)Low-dose or high-dose cytarabine (LoDAC) will be administered by intravenous (IV) injections. | Drug | Mitoxantrone Hydrochloride liposome and cytarabine |
Primary outcome
Occurrence of dose-limiting toxicity (DLT)in dose escalation phase
Time frame: The first cycle (28 days)
Adverse events during treatment in dose expansion phase
Time frame: up to 3 years
9 secondary outcomes
Adverse events during treatment in dose escalation phase
Time frame: up to 3 years
Composite CR rate (CRc: CR+CRi) in dose escalation phase
Time frame: up to 3 years
Objective response rate (ORR) in dose escalation phase
Time frame: up to 3 years
Overall survival (OS) in dose escalation phase
Time frame: up to 3 years
Explore maximum tolerated dose (MTD) in dose escalation phase
Time frame: up to 3 years
Composite CR rate (CRc: CR+CRi) in dose expansion phase
Time frame: up to 3 years
Objective response rate (ORR) in dose expansion phase
Time frame: up to 3 years
Overall survival (OS) in dose expansion phase
Time frame: up to 3 years
Explore RP2D in dose expansion phase
Time frame: up to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2021.
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.
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 Hydrochloride liposome injection and Cytarabine (LoDAC) in people with Treatment-naive or Relapsed or Refractory Acute Myeloid Leukemia (AML), run by CSPC ZhongQi Pharmaceutical Technology Co., Ltd. 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 6 inclusion and 16 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 29 Oct 2021. 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 Jishi Wang, Chief doctor (+86-13639089646, Wangjishi9646@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of dose-limiting toxicity (DLT)in dose escalation phase (time frame: The first cycle (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 29 Oct 2021; AzTrials last refreshed its copy on 6 Nov 2026.