Trial Title:
Chi-GVM Regimen for the Treatment of R/R PTCL
NCT ID:
NCT06211881
Condition:
Relapsed/Refractory Peripheral T-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Gemcitabine
Vinorelbine
Mitoxantrone
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:
Chi-GVM
Description:
Chi-GVM regimen (every 21 days is a treatment cycle):
Chidamide 20 mg orally;gemcitabine 1g/m2, twice a week, intravenous infusion on day 1,
vinorelbine 20 mg/m2, infusion on day 1; Mitoxantrone Hydrochloride Liposome12 mg/m2,
intravenous infusion on day 1; Chidamide maintenance therapy: 20 mg orally twice a
week/28 days/cycle.
Arm group label:
Chi-GVM
Other name:
Chidamide Combined With Gemcitabine, Vinorelbine, and Mitoxantrone Hydrochloride Liposome
Summary:
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphoproliferative
diseases caused by mature T cells, accounting for approximately 10% of non-Hodgkin
lymphomas (NHL). PTCLs have a worse prognosis than aggressive B-cell lymphomas; they are
less responsive to standard anthracycline-based chemotherapy regimens and responses are
less durable. In an analysis of 341 patients with newly diagnosed PTCL who received
anthracycline chemotherapy, 3-year PFS and OS rates were 32% and 52%, respectively,
significantly inferior to matched patients with diffuse large B-cell lymphoma (DLBCL).And
patients who received consolidative hematopoietic cell transplantation (HCT) had no
significant benefit. The prognosis of relapsed/refractory (R/R) patients is even worse.
Among the 420 evaluable R/R PTCL patients in the COMPLETE registration study, the median
OS of R/R patients were 29 months and 12 months respectively . There is still no
effective second-line regimen that can improve patient survival, so treatment options
urgently need to be optimized.We designed a randomized, prospective, multi-center phase
II clinical trial to explore the efficacy of chidamide combined with gemcitabine,
vinorelbine and Mitoxantrone Hydrochloride Liposome (Chi-GVM) in the treatment of
patients with R/R PTCL. We expected to further improve ORR, PFS and OS.
Detailed description:
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphoproliferative
diseases caused by mature T cells, accounting for approximately 10% of non-Hodgkin
lymphomas (NHL). Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) is the
most common subtype, accounting for approximately 26%. This was followed by
angioimmunoblastic T-cell lymphoma (AITL; 19%), anaplastic large cell lymphoma (ALCL,
ALK)-positive (7%), ALK-negative (6%), and enteropathy-associated T-cell lymphoma ( EATL)
.
PTCLs have a worse prognosis than aggressive B-cell lymphomas; they are less responsive
to standard anthracycline-based chemotherapy regimens and responses are less durable. In
an analysis of 341 patients with newly diagnosed PTCL who received anthracycline
chemotherapy, 3-year PFS and OS rates were 32% and 52%, respectively, significantly
inferior to matched patients with diffuse large B-cell lymphoma (DLBCL).And patients who
received consolidative hematopoietic cell transplantation (HCT) had no significant
benefit. The prognosis of relapsed/refractory (R/R) patients is even worse. Among the 420
evaluable R/R PTCL patients in the COMPLETE registration study, the median OS of R/R
patients were 29 months and 12 months respectively . There is still no effective
second-line regimen that can improve patient survival, so treatment options urgently need
to be optimized.
Histone deacetylase (HDAC) inhibitors such as belinostat, romidepsin, etc. have been
confirmed to show good efficacy in R/R AITL;Chinise original drug Chidamide is mainly
targeted at Class I HDAC inhibitors (HDACi) of HDAC subtypes 1, 2, and 3 and class IIb
subtype 10 have the regulatory effect on abnormal epigenetic functions of tumors. It
triggers chromatin remodeling by inhibiting related HDAC isoforms to increase the
acetylation level of chromatin histones, resulting in changes in gene expression (ie,
epigenetic changes) targeting multiple signaling pathways, thereby inhibiting tumor cells
cycle, induce apoptosis of tumor cells, and at the same time have overall regulatory
activity on cellular immunity, inducing and enhancing the tumor killing effect mediated
by natural killer cells (NK) and antigen-specific cytotoxic T cells (CTL). Chidamide also
induces tumor stem cell differentiation and reverses the epithelial-mesenchymal
phenotypic transition (EMT) of tumor cells through epigenetic regulation mechanisms,
thereby restoring the sensitivity of drug-resistant tumor cells to drugs and inhibiting
tumor metastasis. play a potential role in recurrence and other aspects. The above unique
mechanism of action characteristics lay the foundation for the combined application of
chidamide and other chemotherapy drugs in tumor treatment. Its phase II clinical study
explored the effectiveness and safety of chidamide monotherapy in patients with R/R PTCL.
The objective response rate (ORR) assessed by the investigators was 29.1%, and the median
duration of response (DOR) was 9.9 months, and is well tolerated.Chidamide has been
included in the medical insurance indications for patients with relapsed or refractory
PTCL who have received at least one systemic chemotherapy in the past. However, single
drug is still not effective in patients with nTFHL and needs to be combined with other
drugs.
Gemcitabine, dexamethasone, and cisplatin (GDP) combined with autologous hematopoietic
stem cell transplantation (ASCT) can effectively treat patients with R/R PTCL, with an
ORR of 72% to 80% and a CR of 47% to 48%. Among patients who subsequently underwent ASCT,
2-year post-transplant OS was 53%. A retrospective analysis showed that the gemcitabine,
vinorelbine, and doxorubicin (GND) regimen was effective and well tolerated in patients
with R/RT cell lymphoma (n=49; 28 patients with PTCL-NOS), with ORR was 65%, the median
OS was 36 months, and the 5-year estimated OS rate was 32%.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. R/R PTCL confirmed by pathological tissue [including peripheral T-cell
lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma
(AITL), and ALK+ anaplastic large cell lymphoma (ALCL) , ALK-ALCL, monotypic
epithelial intestinal T-cell lymphoma (MEITL), etc.], the diagnostic criteria
refer to the 2022 WHO diagnostic criteria; 2. Have had at least one previous
systemic treatment [including chemotherapy, autologous hematopoietic stem cell
transplantation (ASCT) ), etc.] Patients who have no remission or relapse after
remission; 3. Sign written informed consent and be able to comply with the
visits and related procedures specified in the protocol; 4. Whole-body PET/CT
performed 28 days before study enrollment must be At least 1 evaluable or
measurable lesion that meets the Lugano2014 criteria: lymph node lesions,
measurable lymph nodes must have a long diameter >1.5 cm; non-lymph node
lesions, measurable extranodal lesions must have a long diameter >1.0 cm; 5.
ECOG PS score: 0~2; 6. Have adequate organ and bone marrow function, defined as
follows: neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥80
g/L (neutrophil count in patients with bone marrow involvement) The granulocyte
count can be relaxed to ≥1.0×109/L, the platelet count can be relaxed to
≥50×109/L, and the hemoglobin can be relaxed to ≥75 g/L); 7. Liver and renal
function: Serum creatinine (Cr) ≤1.5 times the upper limit of normal values;
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times
the upper limit of normal values (≤5 times the upper limit of normal values for
patients with liver invasion); total bilirubin (TBIL) ) ≤ 1.5 times the upper
limit of normal value (for patients with liver invasion ≤ 3 times the upper
limit of normal value); 8. Expected survival time more than 3 months; 9. Age
18~75 years old.
Exclusion Criteria:
-
1. The subject's previous anti-tumor treatment history meets one of the following
conditions:
1. Those who have received mitoxantrone or Mitoxantrone Hydrochloride Liposome in
the past;
2. Previously received treatment with doxorubicin or other anthracyclines, with a
total cumulative dose of doxorubicin >360 mg/m2 (converted from other
anthracyclines, 1 mg of doxorubicin is equivalent to 2 mg of epirubicin );
3. Patients who have received ASCT within 100 days of first medication, or have
received allogeneic hematopoietic stem cell transplantation (Allo-SCT);
4. Within 4 weeks before using this study drug for the first time, you have
received anti-tumor treatment (including chemotherapy, targeted therapy,
hormone therapy, taking traditional Chinese medicine with anti-tumor activity,
etc.) or participated in other clinical trials and received clinical trial
drugs.
2. Have a hypersensitivity reaction to any study drug or its ingredients; 3.
Uncontrollable systemic diseases (such as advanced infection, uncontrollable
hypertension, diabetes, etc.); 4. Heart function and disease meet one of the
following conditions:
1. Long QTc syndrome or QTc interval >480 ms;
2. Complete left bundle branch block, II or III degree atrioventricular block;
3. Severe, uncontrolled arrhythmia requiring drug treatment;
4. New York Heart Association classification ≥ III;
5. The cardiac left ventricular ejection fraction (LVEF) is less than 50%;
6. Have a history of myocardial infarction, unstable angina, severe unstable
ventricular arrhythmia or any other arrhythmia requiring treatment, clinically
severe pericardial disease, or acute ischemic or active disease within 6 months
before recruitment Electrocardiographic evidence of sexual conduction system
abnormalities.
5. Active infection of hepatitis B and hepatitis C (hepatitis B virus surface
antigen is positive and hepatitis B virus DNA exceeds 1×103 copies/mL;
hepatitis C virus RNA exceeds 1×103 copies/mL); 6. Human immunodeficiency virus
(HIV) infection (HIV antibody positive); 7. Have suffered from other malignant
tumors in the past or at the same time (except for non-melanoma basal cell
carcinoma of the skin, breast/cervical carcinoma in situ and other malignant
tumors that have been effectively controlled without treatment in the past 5
years); 8. Suffer from primary or secondary central nervous system (CNS)
lymphoma or have a history of CNS lymphoma at the time of recruitment; 9.
Pregnant, lactating women and patients of childbearing age who are unwilling to
take contraceptive measures; 10. People with mental disorders/people unable to
obtain informed consent; 11.Those who are judged by the researcher to be
unsuitable to participate in this trial
Gender:
All
Minimum age:
18 Years
Maximum age:
75 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:
October 25, 2023
Completion date:
September 30, 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/NCT06211881
