Relapsed or Refractory Acute Myeloid Leukemia (AML)Phase 1/2NCT05345938
A Study of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia
A Phase 1/2 study testing Mitoxantrone Hydrochloride Liposome in people with Relapsed or Refractory Acute Myeloid Leukemia (AML), run by CSPC ZhongQi Pharmaceutical Technology Co., Ltd. at 1 site in China.
Trial summary
This is a multi-center, open-label, single-arm, phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of mitoxantrone hydrochloride liposome injection in subjects with acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Acute Myeloid Leukemia (AML)
- What is being tested?
- Mitoxantrone Hydrochloride Liposome
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteChina
- Study dates
- 14 Jun 2022to 19 Nov 2022
- 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
- Subjects fully understand, voluntarily participate in this study and sign the informed consent form;
- Age ≥18 years old, male or female;
- Morphological and/or pathological confirmation of relapsed/refractory AML after prior anti-leukemic therapy or newly diagnosed unfit AML (dose expansion stage) , which are judged by the investigator to be unsuitable for intensive chemotherapy;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for subjects with R/R AML or aged over 75 years old, 0-3 for subjects with unfit AML aged 18 to 74 years old;
- The organ function level must meet the following requirements:
- Liver function : Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times normal upper limit (ULN); Total bilirubin ≤1.5 x ULN ( ≤ 3.0 x ULN for subjects with unfit AML); Renal function: Blood creatinine ≤1.5 x ULN (creatinine clearance <45 mL/min for subjects with unfit AML); 6. Subjects and their partners agree to take effective contraception from the date of signing an informed consent to 6 months after the last dose (for example: combined hormone (contain estrogen and progesterone), combining inhibit ovulation, progestin contraception and inhibit ovulation, intrauterine device, intrauterine hormone release system, bilateral vasectomy, bilateral tubal ligation, avoiding sexual behavior, etc.); female subjects must have negative blood HCG (except menopause, hysterectomy or bilateral oophorectomy).
Who cannot join
- 1. AML occurs in any of the following situations:
- Acute promyelocytic leukemia;
- Chronic myeloid leukaemia in blast crisis;
- Central nervous system (CNS) involvement with AML; 2. Subjects has been previously diagnosed with other malignant tumors in the past 5 years (except curable tumors such as basal cell carcinoma of the skin and carcinoma in situ of the cervix); 3. Graft-versus-host disease requiring ongoing treatment and having received more than one allogeneic stem cell transplant.
- 4. History of allergy to mitoxantrone hydrochloride injection or liposomal drugs; 5. Previous treatment with doxorubicin or other anthracycline and a cumulative dose of doxorubicin in excess of 400mg/m^2 (anthracycline equivalent dose calculation: 1 mg doxorubicin =2 mg epirubicin = 2 mg daunorubicin = 0.5 mg idarubicin = 0.45 mg mitoxantrone; Adriamycin liposomes excepted); 6. Received any antineoplastic therapy within 2 weeks prior to initial administration (or within 5 half-lives of the drug). Except for leukocyte lowering therapy (hydroxyurea, leukocyte separation, etc.) and prophylactic intrathecal injection which are over 24 hours prior to administration; 7.The non-hematologic toxicity of previous anti-tumor treatment > Grade 1 based on CTCAE (except for alopecia, skin pigmentation or tolerable events judged by the investigator); 8. 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); 9. Life expectancy < 3 months; 10. Cardiovascular diseases, including but not limited to:
- QTc interval >480 ms or long QTc syndrome in screening;
Show all 11Show fewer
- Complete left bundle branch block, severe atrioventricular block (without pacemaker);
- Requiring treatment of serious and uncontrolled arrhythmias, unstable angina pectoris, valvular disease, etc;
- Have a history of chronic congestive heart failure, New York Heart Association（NYHA）≥3; or persistent cardiomyopathy;
- Uncontrolled hypertension (defined as multiple measurements of systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg under medication control);
- ECG evidence of myocardial infarction, viral myocarditis, history of severe pericardial disease, acute ischemic or active conduction system abnormalities within 6 months prior to screening; 11. Severe thrombosis or thromboembolism in the past 6 months, including but not limited to cerebrovascular accident (including transient ischemic attack, etc.), upper/lower vena cava thrombosis, lower extremity deep vein thrombosis, pulmonary embolism, etc; 12. HBsAg or HBcAb positive, with HBV DNA≥2000 IU/mL, or HCV 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; 13. Subjects are suffering from any other serious and/or uncontrollable disease that, in the judgment of the investigator, may affect the patient's participation in this study (including but not limited to: uncontrolled diabetes, kidney disease requiring dialysis treatment, severe liver diseases, life-threatening autoimmune disease and hemorrhagic disease, drug abuse, nervous system diseases, etc.); 14. Pregnant or lactating female; 15. Not suitable for this study as decided by the investigator due to other reasons
Trial locations and contacts
1 site in 1 country.
China1 site
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430030
About this study
Official title: A Phase I/II Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia
This is a multi-center, open-label, single-arm, phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of mitoxantrone hydrochloride liposome injection in subjects with acute myeloid leukemia (AML).
Read the detailed description
This study will have two stages. Stage 1: Dose escalation, about 9-18 subjects, who are either refractory to induction therapy or have relapsed (R/R) after achieving remission with prior therapy will be recruited. The enrolled subjects will receive Mitoxantrone Hydrochloride Liposome injection in one of three dose-escalation (30 mg/m^2, 36 mg/m^2, 40 mg/m^2) by intravenous infusion (IV), every 28 days (q4w, 1 cycle). If the patient achieves remission (at least PR) after at most 2 cycles of induction, the original regimen of consolidation therapy can be continued for 2-4 cycles, with a total course of no more than 6 cycles. The DLT observation period is 28 days after the first dose in cycle 1, and including the first 28 days treatment cycle. Subjects in Cycle 1 will have PK sampling performed. Stage 2: Dose expansion, about 35-72 subjects with R/R AML or unfit AML will be recruited. The subjects will receive Mitoxantrone Hydrochloride Liposome dose according to the results of stage 1. If the patient achieves remission (at least PR) after at most 2 cycles of induction, the original regimen of consolidation therapy can be continued for 2-4 cycles, with a total course of no more than 6 cycles.
- Being tested
- Mitoxantrone Hydrochloride Liposome
- 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 LiposomeDrug
Also called HE071
Intravenous injection (IV), on day 1 of each 28-day cycle (q4w)
| Study group | Role | What they receive |
|---|---|---|
| Mitoxantrone Hydrochloride Liposome Injection | Experimental | Stage 1: Subjects with R/R AML will receive one of three dose-escalation (30 mg/m^2, 36 mg/m^2, 40 mg/m^2) Mitoxantrone Hydrochloride Liposome, IV, on day 1 of each 28-day cycle (q4w).
Stage 2: Subjects with R/R AML or unfit AML will receive one dose Mitoxantrone Hydrochloride Liposome every 28 days (a cycle) for a maximum of 6 cycles. Receives: Drug: Mitoxantrone Hydrochloride Liposome |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Number of Participants with Dose Limiting Toxicities (DLTs, Stage 1)
Measured: At the end of Cycle 1 (each cycle is 28 days)
CR
Complete remission (CR) rate (Stage 2)
Measured: From the initiation of the first dose to 28 days after the last dose
Secondary outcomes (13)
TEAEs
Treatment-emergent adverse events (TEAEs)
Measured: From the initiation of the first dose to 28 days after the last dose
CR rate
CR rate (Stage 1)
Measured: From the initiation of the first dose to 28 days after the last dose
CRc
Composite complete response (CRc) rate CRc includes CR and CR with incomplete blood recovery (CRi).
Measured: At the end of Cycle 2 (each cycle is 28 days)
ORR
Objective response rate (ORR) Objective response includes CR, CR with CRi , morphologic leukemia-free status (MLFS) and partial remission (PR).
Measured: At the end of Cycle 2 (each cycle is 28 days)
EFS
Event--free survival (EFS)
Measured: up to 36 months
OS
Overall survival (OS)
Measured: From the enrollment to the death of last subject or the end of the clinical trial (up to 36 months)
Tmax
Peak time (Tmax)
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
Cmax
Maximum concentration (Cmax) of Mitoxantrone Hydrochloride Liposome
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
AUC0-t
Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-t) of Mitoxantrone Hydrochloride Liposome
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
AUC0-∞
Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-∞) of Mitoxantrone Hydrochloride Liposome
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
t1/2
Half-time (t1/2） of Mitoxantrone Hydrochloride Liposome
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
CL
Clearance ( CL) of Mitoxantrone Hydrochloride Liposome
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
Vz
Apparent Volume of Distribution ( Vz) of Mitoxantrone Hydrochloride Liposome
Measured: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2022
- Study start14 Jun 2022
- Primary completion19 Nov 2022
- Study completion19 Nov 2022
Why it stopped: Adjust the research strategy.
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 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
- 1 participants (actual)
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
- NCT05345938
- Sponsor's protocol ID
- HE071-029
- Status last verified
- Jan 2022
- First submitted
- 6 Apr 2022
- Last updated
- 23 Feb 2024
- 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 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05345938
- Acronym / sponsor ID
- HE071-029
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Adjust the research strategy.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 19 Nov 2022 (actual)
- Study completion
- 19 Nov 2022 (actual)
- First posted
- 26 Apr 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 is a multi-center, open-label, single-arm, phase I/II study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of mitoxantrone hydrochloride liposome injection in subjects with acute myeloid leukemia (AML).
Detailed description
This study will have two stages. Stage 1: Dose escalation, about 9-18 subjects, who are either refractory to induction therapy or have relapsed (R/R) after achieving remission with prior therapy will be recruited. The enrolled subjects will receive Mitoxantrone Hydrochloride Liposome injection in one of three dose-escalation (30 mg/m^2, 36 mg/m^2, 40 mg/m^2) by intravenous infusion (IV), every 28 days (q4w, 1 cycle). If the patient achieves remission (at least PR) after at most 2 cycles of induction, the original regimen of consolidation therapy can be continued for 2-4 cycles, with a total course of no more than 6 cycles. The DLT observation period is 28 days after the first dose in cycle 1, and including the first 28 days treatment cycle. Subjects in Cycle 1 will have PK sampling performed. Stage 2: Dose expansion, about 35-72 subjects with R/R AML or unfit AML will be recruited. The subjects will receive Mitoxantrone Hydrochloride Liposome dose according to the results of stage 1. If the patient achieves remission (at least PR) after at most 2 cycles of induction, the original regimen of consolidation therapy can be continued for 2-4 cycles, with a total course of no more than 6 cycles.
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 Injection | Experimental | Drug: Mitoxantrone Hydrochloride LiposomeStage 1: Subjects with R/R AML will receive one of three dose-escalation (30 mg/m^2, 36 mg/m^2, 40 mg/m^2) Mitoxantrone Hydrochloride Liposome, IV, on day 1 of each 28-day cycle (q4w). Stage 2: Subjects with R/R AML or unfit AML will receive one dose Mitoxantrone Hydrochloride Liposome every 28 days (a cycle) for a maximum of 6 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subjects fully understand, voluntarily participate in this study and sign the informed consent form;
- Age ≥18 years old, male or female;
- Morphological and/or pathological confirmation of relapsed/refractory AML after prior anti-leukemic therapy or newly diagnosed unfit AML (dose expansion stage) , which are judged by the investigator to be unsuitable for intensive chemotherapy;
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for subjects with R/R AML or aged over 75 years old, 0-3 for subjects with unfit AML aged 18 to 74 years old;
- The organ function level must meet the following requirements:
Key exclusion criteria (11 listed)
- Acute promyelocytic leukemia;
- Chronic myeloid leukaemia in blast crisis;
- Central nervous system (CNS) involvement with AML; 2. Subjects has been previously diagnosed with other malignant tumors in the past 5 years (except curable tumors such as basal cell carcinoma of the skin and carcinoma in situ of the cervix); 3. Graft-versus-host disease requiring ongoing treatment and having received more than one allogeneic stem cell transplant.
- 4. History of allergy to mitoxantrone hydrochloride injection or liposomal drugs; 5. Previous treatment with doxorubicin or other anthracycline and a cumulative dose of doxorubicin in excess of 400mg/m^2 (anthracycline equivalent dose calculation: 1 mg doxorubicin =2 mg epirubicin = 2 mg daunorubicin = 0.5 mg idarubicin = 0.45 mg mitoxantrone; Adriamycin liposomes excepted); 6. Received any antineoplastic therapy within 2 weeks prior to initial administration (or within 5 half-lives of the drug). Except for leukocyte lowering therapy (hydroxyurea, leukocyte separation, etc.) and prophylactic intrathecal injection which are over 24 hours prior to administration; 7.The non-hematologic toxicity of previous anti-tumor treatment > Grade 1 based on CTCAE (except for alopecia, skin pigmentation or tolerable events judged by the investigator); 8. 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); 9. Life expectancy < 3 months; 10. Cardiovascular diseases, including but not limited to:
- QTc interval >480 ms or long QTc syndrome in screening;
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 LiposomeAlso: HE071Intravenous injection (IV), on day 1 of each 28-day cycle (q4w) | Drug | Mitoxantrone Hydrochloride Liposome Injection |
Primary outcome
DLT
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Number of Participants with Dose Limiting Toxicities (DLTs, Stage 1)
CR
Time frame: From the initiation of the first dose to 28 days after the last dose
Complete remission (CR) rate (Stage 2)
13 secondary outcomes
TEAEs
Time frame: From the initiation of the first dose to 28 days after the last dose
CR rate
Time frame: From the initiation of the first dose to 28 days after the last dose
CRc
Time frame: At the end of Cycle 2 (each cycle is 28 days)
ORR
Time frame: At the end of Cycle 2 (each cycle is 28 days)
EFS
Time frame: up to 36 months
OS
Time frame: From the enrollment to the death of last subject or the end of the clinical trial (up to 36 months)
Tmax
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
Cmax
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
AUC0-t
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
AUC0-∞
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
t1/2
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
CL
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
Vz
Time frame: Within 1hour before IV administration of the first cycle to 1hour before the second cycle
Results and safety
The study was stopped early (reason given: Adjust the research strategy.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 in people with 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 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: stopped early, as of the sponsor's last update on 23 Feb 2024. 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?
The study was stopped early (reason given: Adjust the research strategy.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (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 23 Feb 2024.