Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Analgesics

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Etoposide

Mitoxantrone

Rituximab

Ifosfamide

Lenalidomide

Etoposide phosphate

Immunoglobulins

Isophosphamide mustard

Mechlorethamine

Antineoplastic Agents, Immunological

Immunologic Factors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

R-MINE: Rituximab, Isophosphamide, Mitoxantrone hydrochloride liposome, Etoposide

X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide

Mitoxantrone hydrochloride liposome

1.33 g/m2, d1-3(Rescue with equal dose of mesperidine), Cycle 1\~4

Isophosphamide

MCD/BN2 subtype: BTK inhibitor-Orelabrutinib: 150 mg/d, d1-21, Cycle 2\~4

X: Orelabrutinib

EZB subtype: Chidamide: 20 mg/d, d1, d4, d8, d11, Cycle 2\~4

X: Chidamide

TP53 mutation - X: PD-1 monoclonal antibody - Penpulimab: 200mg/d, d0, Cycle 2\~4

X: Penpulimab

Other-X: Lenalidomide: 25mg/d, d1-10, Cycle 2\~4

X: Lenalidomide

Jinhua Liang, M.D

Wei Xu, PhD& MD

Based on the modified R-MINE of mitoxantrone hydrochloride liposome, the corresponding targeted drug (X) was added according to the genotyping detected by second-generation gene sequencing (NGS) to explore the effectiveness and safety of R-MINE+X in the treatment of recurrent/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Compared with traditional mitoxantrone, mitoxantrone liposomes can significantly prolong the survival time of patients and reduce the cardiotoxicity and non-hematological toxicity of anthracycline drugs. At present, there are no studies on the efficacy and safety of R-MINE+X regimen based on molecular typing in the treatment of R/R DLBCL. Therefore, based on NGS, R/R DLBCL was divided into different molecular types (MCD subtype, BN2 subtype, EZB subtype, A53 subtype and other subtype), and on this basis, different molecular types of targeted drugs (X: MCD/BN2 subtype - BTK inhibitor, EZB subtype - Chidamide, A53 subtype - PD-1 monoclonal antibody and other type - lenalidomide) were used to treat R/R DLBCL. The main purpose was to observe the effectiveness and safety of the program in R/R DLBCL.

R-MINE+X in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

An Open, Single-arm, Multi-center Clinical Trial of Molecular Subtype-guided R-MINE+X Regimen in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Objective response rate (ORR) after 4 cycles of R-MINE+X chemotherapy

Complete remission rate(CRR) after 4 cycles of R-MINE+X chemotherapy

Time from reaching CR or PR for the first time to disease progression

from date of inclusion to date of progression, relapse, or death from any cause

from the date of inclusion to date of death, irrespective of cause

The safety of the drug was evaluated by NCI-CTC AE 5.0 standard

The First Affiliated Hospital with Nanjing Medical University

Symptoms and General Pathology

Leukemia

Acute Disease

Hematologic Diseases

Disease Attributes

Acute Graft Versus Host Disease

Anti-Infective Agents

Cytarabine

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Tacrolimus

Busulfan

Semustine

Immunosuppressive Agents

Antimetabolites

Antiviral Agents

Calcineurin Inhibitors

For the M-PTCy group, Mitoxantrone liposomes with 36mg/m2 and Bu 3.2mg/kg -5 to -4, Flu 30mg/m2 -12 to -9, Ara-C 1.5g/m2 -12 to -9，CTX 15mg/kg/d -3 to -2, was used as conditioning regimen, Post Transplant Cyclophosphamide 50 mg/kg IV daily on days +3 and +4.

For the BUCY group, the conditioning regimen involved Ara-C 2g/m2 q12h -8, BU 3.2 mg/kg -7 to -5,CTX 1.8 g/m2 -4 to -3, to prevent GVHD, MTX 15mg/m2 +1d, 10mg/m2 +3,+6,+11,CsA 3mg/kg/d from -8d,MMF 1g q12h from -8d， ATG 2.5mg/kg/d -5 to -2.

Mitoxantrone liposomes with 36mg/m2 and Bu 3.2mg/kg -5 to -4, Flu 30mg/m2 -12 to -9, Ara-C 1.5g/m2 -12 to -9，CTX 15mg/kg/d -3 to -2, was used as conditioning regimen, Post Transplant Cyclophosphamide 50 mg/kg IV daily on days +3 and +4.

mitoxantrone liposome

Control group:the conditioning regimen involved Ara-C 2g/m2 q12h -8, BU 3.2 mg/kg -7 to -5,CTX 1.8 g/m2 -4 to -3, to prevent GVHD, MTX 15mg/m2 +1d, 10mg/m2 +3,+6,+11,CsA 3mg/kg/d from -8d,MMF 1g q12h from -8d， ATG 2.5mg/kg/d -5 to -2.

Ruju Wang, MD

Huizhu Kang, MD

Yue Han

Yue Han, MD/phD

This study intends to evaluate the efficiency and safety of M-PTCy as conditioning regimen in Haploidentical HSCT for Acute Leukemia, so as to provide a new conditioning regimen for allogeneic hematopoietic cell transplantation.

Haploidentical related donor transplantation is now considered an important alternative to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Posttransplant cyclophosphamide (PTCy) has revolutionized Haplo HCT with acceptable rates of engraftment, graft-versus-host disease (GVHD), relapse, and survival.To prolonger PFS, OS and alleviate GVHD, we combined Mitoxantrone liposomes with PTCy as conditioning regimen in allogeneic hematopoietic cell transplantation.

M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia

An Multicenter, Randomized, Controlled, Prospective Clinical Study of Mitoxantrone Liposome Combined With PTCy as Conditioning Regimen in Allo-HSCT in Acute Leukemia

It is defined as the total survival of a patient after CR until the tumor recurrence or death from any cause.

The time from randomization to death from any cause.

The incidence of graft-versus-host disease

The incidencance of cytomegalovirus and Epstein-barr virus infection

The First Affiliated Hospital of Soochow University

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Azacitidine

Daunorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Mitoxantrone hydrochloride liposome 24 mg/m2, IV every 4 weeks, day 1; Ara-Cytarabine 100 mg/m2, IV every 12 h, days 1-7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7;

Daunorubicin 60 mg/m2, intravenously, once daily, days 1 to 3 Ara-Cytarabine 100 mg/m2, IV drip, every 12h, days 1 to 7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7;

Mitoxantrone hydrochloride liposome 24 mg/m2, IV every 4 weeks, day 1; Ara-Cytarabine 100 mg/m2, IV every 12 h, days 1-7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7

mitoxantrone liposome, Ara-Cytarabine and azacitidine

Daunorubicin 60 mg/m2, intravenously, once daily, days 1 to 3; Ara-Cytarabine 100 mg/m2, IV drip, every 12h, days 1 to 7; Azacitidine 100 mg, subcutaneous, once daily, days 1 to 7;

Daunorubicin,Ara-Cytarabine, azacitidine

Fuling Zhou, Doctor

Zhou Fuling, director

Fuling Zhou

Investigator proposed to apply the new dosage form of mitoxantrone hydrochloride liposomes to the clinical treatment of AML, while combining with cytarabine and azacitidine to form the MA+AZA treatment regimen(Mitoxantrone liposome +Ara-Cytarabine+Azacitidine), which would provide an optimal induction treatment regimen for patients with primary AML by comparing with the traditional chemotherapy regimen, DA+AZA (Daunorubicin+Ara-Cytarabine+Azacitidine).

In this study, AML patients were randomly divided into MA+AZA treatment group and DA+AZA treatment group by conducting a prospective, multicentre, exploratory, randomised controlled study. By observing the efficacy and safety of the MA+AZA combination regimen in the treatment of primary AML, and comparing the superiority of the traditional regimen, high-quality clinical evidence was obtained, providing practical evidence to support the improvement of the intervention effect and clinical prognosis of primary AML.

MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)

A Prospective, Multicenter, Randomized Controlled Study on the MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)

Bone marrow primitive cells \<5%, no primitive cells with Auer vesicles, no primitive cells in the peripheral blood, no extramedullary leukaemia, neutrophil count ≥1.0×109/L, platelet count ≥100×109/L.

Incidence of adverse events, e.g., GI adverse reactions, cardiotoxicity, etc.

Patients not meeting criteria for CR, CRi, MLFS or PR

From the date of the patient's first dose to the date of treatment failure,haematological relapse after CR/CRi or all-cause mortality, whichever occurs first

For patients achieving CR or CRi only, from the date of achieving remission to the date of relapse or death from any cause

The time from the patient's first dose of medication to the time of death from any cause.

Early deaths: all-cause deaths within the timeframe associated with study treatment (e.g., 30 days, 60 days after starting treatment); Cumulative deaths: deaths within the period from the date of achieving remission to the date of no prior relapse for patients achieving CR or CRi only.

Ruijin Hospital

Shanxi Province Cancer Hospital

The First Affiliated Hospital of Zhengzhou University

Jingzhou Central Hospital

Yichang Central People's Hospital

Taihe Hospital

The Central Hospital of Xiaogan

Xianning Central Hospital

The First People's Hospital of Jingzhou

Zhongnan Hospital

Venetoclax

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.

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

Mitoxantrone liposome

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

Hui Zeng, M.D

Huien Zhan, M.M.

Hui Zeng, MD

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.

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).

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

Clinical Study of Venetoclax Combined With Mitoxantrone Liposome in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

To evaluate the tolerability of mitoxantrone liposomes combination regime

To evaluate the efficacy of anti-leukemia

To identify the incidence of AE and SAE in clinical trial

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
R-MINE+X in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma	NCT05784987	Diffuse Large B...	Rituximab Mitoxantrone hy... Isophosphamide Etoposide X: Orelabrutini... X: Chidamide X: Penpulimab X: Lenalidomide	18 Years - 75 Years	The First Affiliated Hospital with Nanjing Medical University
M-PTCy vs BuCy in Haploidentical HSCT for Acute Leukemia	NCT05739630	Acute Leukemia	mitoxantrone li... ATG	14 Years - 60 Years	The First Affiliated Hospital of Soochow University
MA+AZA Regimen for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)	NCT06345365	Acute Myeloid L...	mitoxantrone li... Daunorubicin,Ar...	18 Years - 75 Years	Zhongnan Hospital
Clinical Study of Mitoxantrone Hydrochloride Liposome Injection in Subjects With Acute Myeloid Leukemia	NCT05522192	Relapsed or Ref...	Mitoxantrone li... Venetoclax	18 Years - 75 Years	First Affiliated Hospital of Jinan University

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