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

NCT05784987 | Unknown

• 1 other identifier: CSPC-DED-DLBCL-K09
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Diffuse Large B-cell Lymphoma

Keywords

DLBCL; R-MINE+X; Mitoxantrone liposome

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate(ORR)

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

  up to 4 cycles of chemotherapy(each cycle is 21 days)

Secondary Outcomes (5)

• Complete remission rate(CRR)

  up to 4 cycles of chemotherapy(each cycle is 21 days)

• Duration of remission(DOR)

  up to 4 cycles of chemotherapy(each cycle is 21 days)

• Progression-Free-Survival rate

  1 year

• Overall survival rate

  1 year

• Adverse events (AE)

  From the first day of medication to 28 days after the last dose

Study Arms (1)

R-MINE+X

EXPERIMENTAL

R-MINE: Rituximab, Isophosphamide, Mitoxantrone hydrochloride liposome, Etoposide X: Orelabrutinib, Chidamide, Penpulimab, Lenalidomide

Drug: Rituximab; Drug: Mitoxantrone hydrochloride liposome; Drug: Isophosphamide; Drug: Etoposide; Drug: X: Orelabrutinib; Drug: X: Chidamide; Drug: X: Penpulimab; Drug: X: Lenalidomide

Interventions

Rituximab DRUG

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

R-MINE+X

Mitoxantrone hydrochloride liposome DRUG

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

R-MINE+X

Isophosphamide DRUG

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

R-MINE+X

Etoposide DRUG

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

R-MINE+X

X: Orelabrutinib DRUG

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

R-MINE+X

X: Chidamide DRUG

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

R-MINE+X

X: Penpulimab DRUG

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

R-MINE+X

X: Lenalidomide DRUG

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

R-MINE+X

Eligibility Criteria

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

You may qualify if:

• Join the study voluntarily and sign the informed consent;
• Age ≤ 18 years old ≤75 years old;
• Expected survival time ≥3 months;
• Recurrent or refractory diffuse large B-cell lymphoma confirmed by histopathology;
• 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;
• 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;
• ECOG score 0-2;
• 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);
• 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);

You may not qualify if:

• The subject's previous history of antitumor therapy meets one of the following conditions:
• Previous recipients of mitoxantrone or mitoxantrone liposomes;
• Prior treatment with doxorubicin or anthracycline with a cumulative dose of doxorubicin \> 360 mg/m2 (1 mg of doxorubicin for other anthracyclines);
• Patients who had received autologous hematopoietic stem cell transplantation or had received allogeneic hematopoietic stem cell transplantation within 100 days of the first medication;
• 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;
• Hypersensitivity to any investigational drug or its components;
• Uncontrolled systemic diseases (such as advanced infections, uncontrolled hypertension, diabetes, etc.);
• Cardiac function and disease conform to one of the following conditions:
• Long QTc syndrome or QTc interval \>480 ms;
• Complete left bundle branch block, complete right bundle branch block with left anterior branch block, second degree type II, or third degree atrioventricular block;
• severe, uncontrolled arrhythmias requiring medical treatment;
• New York College of Cardiology Grade ≥ III;
• 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.
• 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);
• Human immunodeficiency virus (HIV) infection (HIV antibody positive);

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Ifosfamide; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Wei Xu, PhD& MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinhua Liang, M.D

CONTACT

15952032421; 1151525490@qq.com

Wei Xu, PhD& MD

CONTACT

862568136034; xuwei10000@hotmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 27, 2023
• Study Start: April 15, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2025
• Last Updated: March 27, 2023

Record last verified: 2023-03