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

NCT ID: NCT05784987

Last Updated: 2023-03-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-15
• Study Completion Date: 2025-01-01

Brief Summary

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).

Detailed Description

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.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-MINE+X

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

X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

375 mg/m2, d0, Cycle 1\~4

Mitoxantrone hydrochloride liposome

Intervention Type: DRUG

20 mg/m2, d1, Cycle 1\~4

Isophosphamide

Intervention Type: DRUG

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

Etoposide

Intervention Type: DRUG

65 mg/m2, d1-3, Cycle 1\~4

X: Orelabrutinib

Intervention Type: DRUG

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

X: Chidamide

Intervention Type: DRUG

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

X: Penpulimab

Intervention Type: DRUG

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

X: Lenalidomide

Intervention Type: DRUG

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

Interventions

Rituximab

375 mg/m2, d0, Cycle 1\~4

Intervention Type: DRUG

Mitoxantrone hydrochloride liposome

20 mg/m2, d1, Cycle 1\~4

Intervention Type: DRUG

Isophosphamide

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

Intervention Type: DRUG

Etoposide

65 mg/m2, d1-3, Cycle 1\~4

Intervention Type: DRUG

X: Orelabrutinib

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

Intervention Type: DRUG

X: Chidamide

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

Intervention Type: DRUG

X: Penpulimab

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

Intervention Type: DRUG

X: Lenalidomide

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Join the study voluntarily and sign the informed consent;

2. Age ≤ 18 years old ≤75 years old;

3. Expected survival time ≥3 months;

4. Recurrent or refractory diffuse large B-cell lymphoma confirmed by histopathology;

5. Consistent with relapsed or refractory lymphoma: Relapsed lymphoma refers to lymphoma that relapsed after CR obtained from initial chemotherapy. Refractory lymphoma is diagnosed by meeting any of the following criteria: 1) tumor shrinkage < 50% or progression after 4 courses of chemotherapy prescribed by the standard regimen; 2) CR was achieved by standard chemotherapy, but recurrent within half a year; 3) Relapse for two or more times after CR; 4) Recurrence after hematopoietic stem cell transplantation;

6. There must be at least one evaluable or measurable lesion in line with Lugano2014 criteria: lymph node lesion, the length and diameter of detectable lymph node must be greater than 1.5cm; For non-lymph node lesions, the diameter of extrinsic lesions should be > 1.0cm;

7. ECOG score 0-2;

8. Bone marrow function: neutrophil count ≥1.5×10^9/L, platelet count ≥75×10^9/L, hemoglobin ≥80g/L (neutrophil count ≥1.0×10^9/L, platelet count ≥50×10^9/L, hemoglobin ≥75g/L in patients with bone marrow involvement);

9. Liver and kidney function: serum creatinine ≤1.5 times the upper limit of normal value; AST and ALT ≤2.5 times the upper limit of normal value (≤5 times the upper limit of normal value for patients with liver invasion); Total bilirubin ≤1.5 times the upper limit of normal value (≤3 times the upper limit of normal value for patients with liver invasion);

Exclusion Criteria

1. The subject's previous history of antitumor therapy meets one of the following conditions:

1. Previous recipients of mitoxantrone or mitoxantrone liposomes;

2. Prior treatment with doxorubicin or anthracycline with a cumulative dose of doxorubicin > 360 mg/m2 (1 mg of doxorubicin for other anthracyclines);

3. Patients who had received autologous hematopoietic stem cell transplantation or had received allogeneic hematopoietic stem cell transplantation within 100 days of the first medication;

4. Received anti-tumor therapy (including chemotherapy, targeted therapy, hormone therapy, taking anti-tumor active Chinese medicine, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the drug in this study;

2. Hypersensitivity to any investigational drug or its components;

3. Uncontrolled systemic diseases (such as advanced infections, uncontrolled hypertension, diabetes, etc.);

4. Cardiac function and disease conform to one of the following conditions:

1. Long QTc syndrome or QTc interval >480 ms;

2. Complete left bundle branch block, complete right bundle branch block with left anterior branch block, second degree type II, or third degree atrioventricular block;

3. severe, uncontrolled arrhythmias requiring medical treatment;

4. New York College of Cardiology Grade ≥ III;

5. A history of acute myocardial infarction, unstable angina pectoris, severely unstable ventricular arrhythmias or any other arrhythmia requiring treatment, a history of clinically severe pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction abnormalities within the 6 months prior to recruitment.

5. Hepatitis B and hepatitis C active infection (hepatitis B virus surface antigen positive and hepatitis B virus DNA more than 1x10^3 copies /mL; HCV RNA over 1x10^3 copies /mL);

6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);

7. Past or present co-existing malignancies (in addition to non-melanoma basal cell carcinoma of the skin, carcinoma in situ of the breast/cervix, and other malignancies that have been effectively controlled without treatment in the past five years);

8. Primary or secondary central nervous system (CNS) lymphoma or history of CNS lymphoma at the time of recruitment;

9. There is significant gastrointestinal disease at the time of screening that may affect drug intake, transport or absorption (e.g. inability to swallow, chronic diarrhea, intestinal obstruction, etc.);

10. Pregnant and lactating women and patients of childbearing age who do not wish to take contraceptive measures;

11. Situations in which other researchers have determined that participation in this study is not appropriate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Xu, PhD& MD

Role: PRINCIPAL_INVESTIGATOR

The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)

Central Contacts

Jinhua Liang, M.D

Role: CONTACT

1151525490@qq.com

15952032421

Wei Xu, PhD& MD

Role: CONTACT

xuwei10000@hotmail.com

862568136034

Other Identifiers

CSPC-DED-DLBCL-K09

Identifier Type: -

Identifier Source: org_study_id