Diffuse Large B-cell Lymphoma
Conditions
Keywords
DLBCL, R-MINE+X, Mitoxantrone liposome
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.
Interventions
DRUGRituximab
375 mg/m2, d0, Cycle 1\ 4
DRUGMitoxantrone hydrochloride liposome
20 mg/m2, d1, Cycle 1\ 4
DRUGIsophosphamide
1.33 g/m2, d1-3(Rescue with equal dose of mesperidine), Cycle 1\ 4
DRUGEtoposide
65 mg/m2, d1-3, Cycle 1\ 4
DRUGX: Orelabrutinib
MCD/BN2 subtype: BTK inhibitor-Orelabrutinib: 150 mg/d, d1-21, Cycle 2\ 4
DRUGX: Chidamide
EZB subtype: Chidamide: 20 mg/d, d1, d4, d8, d11, Cycle 2\ 4
DRUGX: Penpulimab
TP53 mutation - X: PD-1 monoclonal antibody - Penpulimab: 200mg/d, d0, Cycle 2\ 4
DRUGX: Lenalidomide
Other-X: Lenalidomide: 25mg/d, d1-10, Cycle 2\ 4
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Progression-Free-Survival rate | 1 year | from date of inclusion to date of progression, relapse, or death from any cause |
| Overall survival rate | 1 year | from the date of inclusion to date of death, irrespective of cause |
| 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 |
Contacts
Primary ContactJinhua Liang, M.D
Backup ContactWei Xu, PhD& MD
Outcome results
None listed