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

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05784987
• Other study ID #: CSPC-DED-DLBCL-K09
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 15, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: March 2023
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Jinhua Liang, M.D
• Phone: 15952032421
• Email: 1151525490[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Rituximab
375 mg/m2, d0, Cycle 1~4
• Mitoxantrone hydrochloride liposome
20 mg/m2, d1, Cycle 1~4
• Isophosphamide
1.33 g/m2, d1-3(Rescue with equal dose of mesperidine), Cycle 1~4
• Etoposide
65 mg/m2, d1-3, Cycle 1~4
• X: Orelabrutinib
MCD/BN2 subtype: BTK inhibitor-Orelabrutinib: 150 mg/d, d1-21, Cycle 2~4
• X: Chidamide
EZB subtype: Chidamide: 20 mg/d, d1, d4, d8, d11, Cycle 2~4
• X: Penpulimab
TP53 mutation - X: PD-1 monoclonal antibody - Penpulimab: 200mg/d, d0, Cycle 2~4
• X: Lenalidomide
Other-X: Lenalidomide: 25mg/d, d1-10, Cycle 2~4

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Outcome

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