Clinical Study of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia

NCT05522192 | Recruiting Phase 1 DMC

• 1 other identifier: CSPC-DED-AML-K04
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia

Keywords

venetoclax; Mitoxantrone liposomes; Acute myeloid leukemia

Outcome Measures

Primary Outcomes (2)

• Phase I: MTD of mitoxantrone liposomes

  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)

  To evaluate the efficacy of anti-leukemia

  At the end of Cycle 2 (each cycle is 28 days)

Secondary Outcomes (9)

• Phase I: Composite complete remission rate (CRc)

  At the end of Cycle 2 (each cycle is 28 days)

• Phase I: Objective response rate (ORR)

  At the end of Cycle 2 (each cycle is 28 days)

• Phase I: Relapse free survival (RFS)

  Up to 2 years

• Phase I: Overall survival (OS)

  Up to 2 years

• Phase I: Safety: Hematologic and non-hematologic toxicities (NCI CTCAE v5.0)

  From the initiation of the first dose to 28 days after the last dose

Study Arms (1)

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.

Drug: Mitoxantrone liposome; Drug: Venetoclax

Interventions

Mitoxantrone liposome DRUG

Phase I: 24mg/m2, 30 mg/m2, 36mg/m2, IV, d1; Phase II: RP2D.

Also known as: Mitoxantrone Hydrochloride Liposome Injection

Venetoclax-Mitoxantrone liposome

Venetoclax DRUG

Phase I/II: 100mg po d1，200mg po d2，400mg po d3-28.

Also known as: Venclexta

Venetoclax-Mitoxantrone liposome

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hui Zeng: lead
• CSPC Ouyi Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

First Affiliated Hospital of Jinan University

Guangzhou, Guangdong, 510632, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Hui Zeng, M.D

  First Affiliated Hospital of Jinan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hui Zeng, M.D

CONTACT

+86-18002201919; xyzengh@hotmail.com

Huien Zhan, M.M.

CONTACT

+86-19926098944; zhanhuien@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: August 12, 2022
• First Posted: August 30, 2022
• Study Start: July 21, 2022
• Primary Completion: November 1, 2025
• Study Completion: May 1, 2026
• Last Updated: August 30, 2022

Record last verified: 2022-08

Locations

CN (1)