Trial Title:
R-MINE+X in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
NCT ID:
NCT05784987
Condition:
Diffuse Large B-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Rituximab
Etoposide
Lenalidomide
Mitoxantrone
Ifosfamide
Isophosphamide mustard
Conditions: Keywords:
DLBCL
R-MINE+X
Mitoxantrone liposome
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Rituximab
Description:
375 mg/m2, d0, Cycle 1~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
Mitoxantrone hydrochloride liposome
Description:
20 mg/m2, d1, Cycle 1~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
Isophosphamide
Description:
1.33 g/m2, d1-3(Rescue with equal dose of mesperidine), Cycle 1~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
Etoposide
Description:
65 mg/m2, d1-3, Cycle 1~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
X: Orelabrutinib
Description:
MCD/BN2 subtype: BTK inhibitor-Orelabrutinib: 150 mg/d, d1-21, Cycle 2~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
X: Chidamide
Description:
EZB subtype: Chidamide: 20 mg/d, d1, d4, d8, d11, Cycle 2~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
X: Penpulimab
Description:
TP53 mutation - X: PD-1 monoclonal antibody - Penpulimab: 200mg/d, d0, Cycle 2~4
Arm group label:
R-MINE+X
Intervention type:
Drug
Intervention name:
X: Lenalidomide
Description:
Other-X: Lenalidomide: 25mg/d, d1-10, Cycle 2~4
Arm group label:
R-MINE+X
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
April 15, 2023
Completion date:
January 1, 2025
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05784987
