Trial Title:
CMOP Regimen and Chidamide in the Treatment of Newly Diagnosed Peripheral T-cell Lymphoma
NCT ID:
NCT05896813
Condition:
Newly Diagnosed Peripheral T-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CMOP+Chidamide
Description:
Cyclophosphamide: 750 mg/m2, d1; Mitoxantrone Hydrochloride Liposome: 20 mg/m2, d1;
Vincristine: 1.4 g/m2, d1 (maximum dose of 2 mg), or vindesine 3 mg/m2, d1; Prednisone:
60 mg/m2, d1-d5; Chidamide:20 mg, biw. The treatment is administered every 3 weeks as a
cycle and lasts for a total of 6 cycles.
Arm group label:
CMOP+Chi
Summary:
Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous and aggressive non-Hodgkin's
lymphoma. The incidence rate of PTCL in China is much higher than the global average, and
there is no unified standard treatment for initial PTCL. Currently, the CHOP regimen is
widely used as first-line treatment. However, the overall response rate is still low, and
effective therapies need to be explored. Epigenetics and genetics jointly determine
critical features of tumors, and exploring new treatment strategies and developing
targeted drugs based on deep understanding of the pathogenesis is of significant
importance. The combined application of DNMT inhibitors and HDAC inhibitors has strong
scientific support. The Phase II clinical study of Mitoxantrone Hydrochloride Liposome in
treating relapsed or refractory PTCL achieved positive results and regulatory approval.
The CMOP regimen combining Mitoxantrone Hydrochloride Liposome with Chidamide is worth
exploring for initial PTCL treatment.
Detailed description:
Peripheral T-cell lymphoma (PTCL) originates from mature thymic T-cells and is a highly
heterogeneous and aggressive non-Hodgkin's lymphoma (NHL). The 2016 revised WHO
classification divides PTCL into 4 major categories with over 30 subtypes, including
common subtypes such as anaplastic large-cell lymphoma (ALCL), ALK-positive/+ and
ALK-negative/-, angioimmunoblastic T-cell lymphoma (AITL), and PTCL, not otherwise
specified (PTCL-NOS) . In 2020, the estimated global incidence of new NHL patients was
over 540,000, with over 90,000 cases in China. Compared with B-cell lymphomas, PTCL has a
lower incidence rate, but PTCL patients' proportion in China is significantly higher than
in Western countries at approximately 21% . The incidence rate of PTCL in China accounts
for nearly 21% of NHL, much higher than the global average .
Currently, there is no unified standard treatment for initial PTCL. The National
Comprehensive Cancer Network (NCCN) guidelines in the US and the Chinese Society of
Clinical Oncology (CSCO) recommend using the CHOP regimen (cyclophosphamide, doxorubicin,
vincristine, and prednisone) as first-line treatment . However, the CHOP regimen is
mainly based on treatment experience with B-cell lymphomas, and more effective therapies
need to be explored. Over the past few decades, research progress in both basic and
clinical aspects of PTCL has been slow, with poor treatment outcomes. The overall
response rate of first-line treatment is 50%-70%. Except for ALCL, ALK(+), PTCL patients
receiving induction therapy are suggested to undergo autologous hematopoietic stem cell
transplantation (ASCT) treatment, yet even so, the overall response rate is still low,
with a poor prognosis. Except for ALCL, ALK+ patients, the five-year overall survival
(OS) rate of other subtypes is less than 50% , and PTCL patients are prone to relapse ,
with a three-year OS probability of about 20% .
The overall treatment effect for PTCL patients is still not ideal, and their prognosis
has not improved over the past few decades. Patients often relapse early, with a shorter
progression-free survival (PFS) and OS. Genetic mutations, variations, and tumor
occurrence and development are closely related, and the same is true for epigenetic
regulation. Epigenetics and genetics jointly determine critical features of a tumor:
heterogeneity, plasticity, stem cell-like properties, and immune escape. As lymphomas
often have epigenetic mutations, exploring new treatment strategies and developing
targeted drugs based on a deep understanding of the pathogenesis is of significant
importance in improving the efficacy of PTCL treatment.
Since both highly methylated DNA and low acetylated histones can lead to a closed
chromatin state by independent mechanisms, resulting in the silencing of tumor suppressor
genes , the combined application of DNMT inhibitors and HDAC inhibitors has strong
scientific support. Both DNMT inhibitors and HDAC inhibitors have a chemosensitizing
effect. Acetylation changes the chromatin structure, plays a role in regulating
epigenetics as well as in chemotherapy sensitization, while DNMT inhibitors can enhance
the sensitivity of lymphoma resistant to chemotherapy. Currently, the combination of
AZA+HDACi in epigenetic treatments has been explored for lymphoma treatment.
In the Phase II clinical study of Mitoxantrone Hydrochloride Liposome, 108 patients with
relapsed or refractory PTCL were treated with Mitoxantrone Hydrochloride Liposome alone,
achieving an objective response rate (ORR) of 41.7% (32.3%, 51.5%) and a complete
response rate (CRR) of 23.1% (25/108). The median PFS was 8.5 months, and the median OS
was 22.8 months. The treatment was well-tolerated and efficacious, resulting in
regulatory approval for Mitoxantrone Hydrochloride Liposome in treating relapsed or
refractory PTCL adult patients . Based on this, the CMOP regimen, which is based on
Mitoxantrone Hydrochloride Liposome combined with Chidamide, is worth exploring for
initial PTCL treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient understands the content of this study, voluntarily participates in the
study, and signs the informed consent form (ICF);
2. Age: 18-80 years;
3. Expected survival time ≥ 3 months;
4. Histologically confirmed PTCL, one of the following subtypes:
1. PTCL not otherwise specified (PTCL-NOS)
2. Nodal T follicular helper (Tfh) cell lymphoma
3. Other subtypes of PTCL that the researcher deems eligible for inclusion in the
study;
5. At least one measurable or evaluable lesion that meets the Lugano2014 criteria: for
lymph node lesions, the longest diameter should be >1.5 cm, and for extranodal
lesions, the longest diameter should be >1.0 cm;
6. ECOG score 0-2 points;
7. Bone marrow function: neutrophil count ≥ 1.5×109/L, platelet count ≥ 75×109/L,
hemoglobin ≥ 80 g/L (for patients with bone marrow involvement, the neutrophil count
can be relaxed to ≥ 1.0×109/L, platelet count can be relaxed to ≥ 50×109/L,
hemoglobin can be relaxed to ≥ 75 g/L);
8. Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal,
AST and ALT ≤ 2.5 times the upper limit of normal (≤ 5 times the upper limit of
normal for patients with liver involvement), and total bilirubin ≤ 1.5 times the
upper limit of normal (≤ 3 times the upper limit of normal for patients with liver
involvement).
Exclusion Criteria:
-
1. Hypersensitivity to any study drug or its components; 2. Uncontrollable
systemic diseases (such as advanced infection, uncontrolled hypertension,
diabetes, etc.); 3. One of the following applies to cardiac function and
disease:
1. Long QT syndrome or QTc interval >480 ms;
2. Complete left bundle branch block, II or III degree atrioventricular block;
3. Severe, uncontrolled arrhythmia requiring medication;
4. New York Heart Association (NYHA) grade ≥ III;
5. Left ventricular ejection fraction (LVEF) <50%;
6. A history of acute myocardial infarction, unstable angina, severe unstable
ventricular arrhythmia, or other arrhythmias or clinically significant
pericardial disease requiring treatment within the six months prior to
recruitment or evidence of acute ischemic or active conduction system
abnormalities on the electrocardiogram; 4. Active hepatitis B or C infection
(hepatitis B surface antigen positive and hepatitis B virus DNA > 1x104
copies/mL; hepatitis C virus RNA > 1x104 copies/mL); 5. Human immunodeficiency
virus (HIV) infection (HIV antibody positive); 6. Previously or currently
diagnosed with other malignant tumors (except for non-melanoma skin basal cell
carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that
have not been treated and effectively controlled within the past five years);
7. Central nervous system (CNS) lymphoma or a history of CNS lymphoma; 8.
Pregnant or lactating women and childbearing patients who do not want to take
contraceptive measures; 9. Other situations judged by the researcher to be
unsuitable for participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Hematological Department, People's Hospital of Jiangsu Province
Address:
City:
Nanjing
Zip:
210029
Country:
China
Status:
Recruiting
Contact:
Last name:
Wei Xu, PhD
Phone:
+86-2568302182
Email:
xuwei10000@hotmail.com
Start date:
March 1, 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/NCT05896813
