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

Not Applicable

Not yet recruiting

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Drug: Rituximab; Drug: Mitoxantrone hydrochloride liposome; Drug: Isophosphamide; Drug: Etoposide

• Registration Number: NCT05784987
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

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...

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Status Verified: 2023-03
• Study First Submitted: 2023-03-02
• Study First Submitted QC: 2023-03-23
• Last Update Submitted: 2023-03-23
• Study First Posted: 2023-03-27
• Last Update Posted: 2023-03-27
• Study Start: 2023-04-15
• Primary Completion: 2024-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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);

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate(ORR)	up to 4 cycles of chemotherapy(each cycle is 21 days)	Objective response rate (ORR) after 4 cycles of R-MINE+X chemotherapy

Secondary Outcome Measures

Name	Time	Method
Adverse events (AE)	From the first day of medication to 28 days after the last dose	The safety of the drug was evaluated by NCI-CTC AE 5.0 standard
Complete remission rate(CRR)	up to 4 cycles of chemotherapy(each cycle is 21 days)	Complete remission rate(CRR) after 4 cycles of R-MINE+X chemotherapy
Duration of remission(DOR)	up to 4 cycles of chemotherapy(each cycle is 21 days)	Time from reaching CR or PR for the first time to disease progression
Overall survival rate	1 year	from the date of inclusion to date of death, irrespective of cause
Progression-Free-Survival rate	1 year	from date of inclusion to date of progression, relapse, or death from any cause