## Protocol Section
### Identification Module
**NCT ID:** NCT06434662

**Brief Title:** Mitoxantrone Hydrochloride Liposome Injection, Cytarabine Combined With Venetoclax in the Treatment of R/R AML

**Official Title:** A Phase II Study of the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Injection, Cytarabine and Venetoclax in Patients With Relapsed/Refractory AML

#### Organization Study ID Info
**ID:** CSPC-DED-AML-K13
#### Organization
**Class:** OTHER
**Full Name:** First Affiliated Hospital of Zhejiang University
### Status Module
#### Completion Date
**Date:** 2026-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-02-29

**Type:** ACTUAL

**Status Verified Date:** 2024-03

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

#### Lead Sponsor

**Class:** OTHER

**Name:** First Affiliated Hospital of Zhejiang University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The goal of this study is to evaluate the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome injection, cytarabine and venetoclax (MAV) in the treatment of relapsed or refractory (R/R) AML. It will also tentatively explore the correlation between different biological characteristics and therapeutic efficacy. The main questions it aims to answer are:Dose the combination regimen of MAV enhanced the composite complete remission in R/R AML? Participants will receive laboratory tests of bone marrow and blood specimens at regular times after MAV treatment.

**Detailed Description:** Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy with a poor prognosis. The "3+7" regimen, combining anthracyclines with cytarabine, remains the standard treatment for first line treatment. However, about 20% of patients will develop into primary refractory disease, and more than 50% of patients who achieved complete remission will eventually relapse. For patients with R/R AML, there is currently no established standard treatment. Combining the third drugs with "3+7" regimen is one of the clinical exploration directions.

The purpose of this prospective, single-center, single-arm, pahse II study is to evaluate the efficacy and safety of a combination regimen of mitoxantrone hydrochloride liposome injection, cytarabine and venetoclax in the treatment of R/R AML. All participants will receive MAV treatment including 24 mg/m2 mitoxantrone hydrochloride liposome on day 1, 1.0 g/m2 q12h cytarabine on day 1,3,5 and 400 mg venetoclax on day 2-10 with a dose escalation on day 2-4. Each cycle consists of 4 weeks. A maximum of 2 cycles of therapy are planned.

### Conditions Module

**Conditions:**

- Relapsed/Refractory Acute Myeloid Leukaemia

- Myeloid Malignancy

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 34

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** mitoxantrone hydrochloride liposome injection, cytarabine combined with venetoclax

**Intervention Names:**

- Drug: mitoxantrone hydrochloride liposome

- Drug: Cytarabine

- Drug: Venetoclax

**Label:** MAV regimen

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- MAV regimen

**Description:** Mitoxantrone hydrochloride liposome (24 mg/m\^2) on day 1, every 4 weeks

**Name:** mitoxantrone hydrochloride liposome

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- MAV regimen

**Description:** Cytarabine (1.0 g/m\^2, q12h ) on day 1,3,5, every 4 weeks

**Name:** Cytarabine

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- MAV regimen

**Description:** Venetoclax 100 mg on day 2，200 mg on day 3，400 mg on day 4-10, every 4 weeks

**Name:** Venetoclax

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Blast rate lower than 5% with or without peripheral blood cell recover

**Measure:** Composite complete remission (CRc) rate

**Time Frame:** At the end of each cycle (each cycle is 28 days), up to 2 cycles

#### Secondary Outcomes

**Description:** Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria

**Measure:** Overall response rate (ORR)

**Time Frame:** At the end of each cycle (each cycle is 28 days), up to 2 cycles

**Description:** Defined only for patients achieving CR or CRi; measured from the date of achievement of remission until the date of hematologic relapse or death from any cause;

**Measure:** Relapsed free survival (RFS)

**Time Frame:** up to 12 months

**Description:** Defined for all patients in a trial; measured from day 1 of treatment to the date of treatment failure, hematologic relapse from CR/CRi or death from any cause, whichever occurs first;

**Measure:** Event free survival (EFS)

**Time Frame:** up to 12 months

**Description:** Defined for all patients in a trial; measured from day 1 of treatment to the date of death from any cause;

**Measure:** overall survival (OS)

**Time Frame:** up to 12 months

**Description:** Percentage of participants who achieve a CR MRD- as defined by investigators based on ELN 2022 criteria; MRD level is detected by flow cytometry which value \<0.1% is defined as negtive;

**Measure:** Rate of CR without minimal residual disease (CR MRD-)

**Time Frame:** At the end of each cycle (each cycle is 28 days), up to 2 cycles

**Description:** The safety of the drug was evaluated by NCI-CTC AE 5.0 standard.Hematologic and non-hematologic toxicity.

**Measure:** Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

**Time Frame:** From day 1 of treatment to 28 days after the last dose

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
2. Age ≥18.
3. Clinically diagnosed relapsed/refractory AML, excluding acute promyelocytic leukemia.

   1. Initial treatment patients who failed after 2 courses of treatment with standard regimen.
   2. Bone marrow blasts≥5% after the first CR/CRi, or reappearance of blasts in the blood in at least 2 peripheral blood samples at least one week apart, or leukemia cell infiltration appeared in extramedullary without treatment.
   3. First conversion from MRD negativity to MRD positivity without treatment.
4. Physical status score of Eastern Oncology Collaboration Group (ECOG) : 0-2.
5. Researchers determined that the patients could tolerate intensive chemotherapy.
6. Life expectancy \> 3 months.
7. AST/ALT≤2.5 ULN (for subjects with hepatic infiltration≤5 ULN); Total bilirubin≤1.5 ULN (for subjects with hepatic infiltration≤3 ULN); Serum creatinine≤1.5 ULN.

Exclusion Criteria:

1. Previous anti-tumor therapy meets one of the following criteria:

   1. Prior therapy with mitoxantrone or mitoxantrone liposome;
   2. Prior therapy with doxorubicin or anthracyclines, and the cumulative dose of doxorubicin \> 360 mg/m\^2 (1 mg doxorubicin was equivalent to 2 mg daunorubicin or 0.5 mg idarubicin);
   3. Have received other anti-tumor therapy (including chemotherapy, targeted therapy, hormone therapy, Chinese medicines with anti-tumor activity, except those that do not affect the efficacy of the study as determined by the investigator) or participated in other clinical trials and received clinical trial drugs within 4 weeks or 5 half-lives of the drug before the study;
2. Cardiovascular diseases, including but not limited to:

   1. QTc interval \>480 ms or long QTc syndrome in screening;
   2. Complete left bundle branch block, 2 or 3 grade atrioventricular block;
   3. Requiring treatment of serious and uncontrolled arrhythmia;
   4. New York Heart Association（NYHA≥3;
   5. Cardiac ejection fraction (EF) was less than 50%;
   6. Myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other history of arrhythmia or clinically serious pericardial disease that requires treatment within the first 6 months of enrollment, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
3. Central nervous system leukemia;
4. Previous or current occurrence of other malignancies (in addition to non-melanoma basal cell carcinoma of the skin that is effectively controlled, breast/cervical carcinoma in situ, and other malignancies that have been effectively controlled without treatment within the past five years).
5. Subjects are suffering from any other uncontrollable disease (including but not limited to: uncontrolled diabetes and hypertension, and advanced infection);
6. HIV infection.
7. HBsAg or HBcAb positive, with HBV-DNA≥1x10\^3 copies/mL; or HCV-RNA≥1x10\^3 copies/mL;
8. A history of immediate or delayed allergy to similar drug and excipients of the investigate drug.
9. Pregnant, lactating female or subjects who refuse to use effective contraception during the study.
10. With a history of severe neurological or psychiatric illness.
11. Not suitable for this study as decided by the investigator.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jiej0503@163.com

**Name:** Jie Jin, M.D.

**Phone:** +86 571-87236896

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Hangzhou

**Contacts:**

***Contact 1:***

- **Email:** jiej0503@163.com

- **Name:** Jie Jin, M.D.

- **Phone:** +86 571-87236896

- **Role:** CONTACT

**Country:** China

**Facility:** The First Affiliated Hospital, Zhejiang University School of Medicine

**State:** Zhejiang

**Status:** RECRUITING

**Zip:** 310003

#### Overall Officials

**Official 1:**

**Affiliation:** Zhejiang University

**Name:** Jie Jin, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: LOW

- As Found: Unknown

- ID: M18127

- Name: Leukemia, Myeloid, Acute

- Relevance: LOW

- As Found: Unknown

- ID: T3995

- Name: Myeloid Leukemia

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: T182

- Name: Acute Myeloid Leukemia

- Relevance: HIGH

- As Found: Acute Myeloid Leukemia

- ID: T188

- Name: Acute Non Lymphoblastic Leukemia

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Ancestors

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000700

- Term: Analgesics

- ID: D000018689

- Term: Sensory System Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000059005

- Term: Topoisomerase II Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Analg

- Name: Analgesics

### Intervention Browse Module - Browse Leaves

- ID: M6766

- Name: Cytarabine

- Relevance: HIGH

- As Found: Multi-

- ID: M249656

- Name: Venetoclax

- Relevance: HIGH

- As Found: Extended

- ID: M11908

- Name: Mitoxantrone

- Relevance: HIGH

- As Found: Ask

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M4032

- Name: Analgesics

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000003561

- Term: Cytarabine

- ID: C000579720

- Term: Venetoclax

- ID: D000008942

- Term: Mitoxantrone

### Misc Info Module

- Version Holder: 2024-05-31
