Trial Title:
Genotype-guided Treatment in Newly Diagnosed PTCL
NCT ID:
NCT05675813
Condition:
Peripheral T Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Azacitidine
Tislelizumab
Conditions: Keywords:
Biomarker-driven
Genetic subtypes
Complete response rate
Phase 1/2
Precision medicine
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
CHOP+selinexor+5-Azacitidine
Description:
Phase I: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50
mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day
PO on days 1-5 of every 21-day cycle for the first cycle. If tumor NGS indicates T1
genetic subtype, for the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1
and selinexor 40mg or 60mg qw (d-7, 1, 8) by traditional "3+3" dose escalation methods
and decide RP2D of selinexor.
Phase II: Patients will receive CHOP for the first cycle. If tumor NGS indicates T1
genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen
for 5 cycles of every 21-day cycle.
Arm group label:
T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP
Intervention type:
Drug
Intervention name:
CHOP+duvelisib+5-Azacitidine
Description:
Phase I: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50
mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day
PO on days 1-5 of every 21-day cycle for the first cycle. If tumor NGS indicates T2
genetic subtype, for the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1
and duvelisib 25mg or 50mg bid (d1-14) by traditional "3+3" dose escalation methods and
decide RP2D of duvelisib.
Phase II: Patients will receive CHOP for the first cycle. If tumor NGS indicates T1
genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen
for 5 cycles of every 21-day cycle.
Arm group label:
T2: CHOP+duvelisib+5-Azacitidine vs CHOP
Intervention type:
Drug
Intervention name:
CHOP+chidamide+tislelizumab
Description:
Phase I: Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50
mg/m² IV, and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day
PO on days 1-5 of every 21-day cycle for the first cycle. If tumor NGS indicates T3
genetic subtype, for the remaining 5 cycles, they will receive tislelizumab 200mg d0
ivgtt and chidamide 20mg or 30mg biw (d1,4,8,11) by traditional "3+3" dose escalation
methods and decide RP2D of chidamide.
Phase II: Patients will receive CHOP for the first cycle. If tumor NGS indicates T3
genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen
for 5 cycles of every 21-day cycle.
Arm group label:
T3: CHOP+chidamide+tislelizumab (CHOPX2)vs CHOP
Intervention type:
Drug
Intervention name:
standard CHOP
Description:
Patients in this arm will receive cyclophosphamide 750 mg/m² IV, doxorubicin 50 mg/m² IV,
and vincristine 1.4 mg/m² IV (maximum 2 mg) on day 1, and prednisone 100 mg/day PO on
days 1-5 of every 21-day cycle for the 6 cycles.
Arm group label:
T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP
Arm group label:
T2: CHOP+duvelisib+5-Azacitidine vs CHOP
Arm group label:
T3: CHOP+chidamide+tislelizumab (CHOPX2)vs CHOP
Summary:
This study includes Phase I and Phase II stages. Phase I is an open-label trial to
confirm RP2D of oral targeted agents in three genetic subtypes. Phase II is a
multicenter, prospective, randomized, open-label, controlled trial to evaluate the
efficacy and safety of genotype-guided targeted agents plus cyclophosphamide,
doxorubicin, vincristine, and prednisone (CHOP-X2) versus cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP) in patients with peripheral T-cell lymphoma.
Detailed description:
Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes.
Standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy
is still the most widely used front-line treatment of PTCL except Brentuximab-CHP
application in anaplastic large cell lymphoma (ALCL). The CR rate ranges from 31%-56% in
different studies with different PTCL histology compositions. With the exception for
ALCL-anaplastic lymphoma kinase (ALK)-positive, the 5-year overall survival (OS) rate is
approximately 30%-40% for most subtypes of PTCL patients in current situation, remaining
as the unmet medical needs in this disease. Based on genetic subtypes in PTCL, and our
previous study exploring targeted agents plus CHOP based on genetic mutations
(Guidance-03 study), we conducted this multicenter, prospective, randomized, open-label,
controlled trial to evaluate the efficacy and safety of genotype-guided targeted agents
plus CHOP (CHOP-X2) versus cyclophosphamide, doxorubicin, vincristine, and prednisone
(CHOP) in patients with PTCL. It includes phase I and phase II stages. Patients will
receceived stardard CHOP for the first cycle and then obtain the genetic subtypes from
tumor NGS befor Cycle 2. In phase I, recommended phase 2 dose (RP2D) of oral targeted
agents will be confirmed by traditional "3+3" dose escalation methods. In phase II,
patients will receive standard CHOP for the first cycle and then 1:1 be randomized to
CHOPX2 or CHOP regimen in each genetic subtypes.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically-confirmed Peripheral T-cell lymphoma
- Availability of archival or freshly collected tumor tissue before study enrollment
enough for NGS
- Evaluable lesion by PET-CT or CT scan
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Life expectancy greater than or equal to (>/=) 3 months
- Informed consent
Exclusion Criteria:
- Patients with ALCL and cutaneous TCL
- Patients with central nervous system (CNS) lymphoma
- History of malignancies except for basal cell or squamous cell carcinoma of the skin
or carcinoma in situ of the cervix
- Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders,
connective tissue diseases, serious infectious diseases and other diseases
- Laboratory measures meet the following criteria at screening (unless caused by
lymphoma):
Neutrophils<1.0×10^9/L Platelets<75×10^9/L (Platelets<50×10^9/L in case of bone marrow
involvement) ALT or AST is 2.5 times higher than the upper limits of normal (ULN), AKP
and bilirubin are 1.5 times higher than the ULN.
Creatinine is 1.5 times higher than the ULN.
- HIV-infected patients
- Active hepatitis infection
- Patients with psychiatric disorders or patients who are known or suspected to be
unable to fully comply with the study protocol
- Pregnant or lactation
- Other medical conditions determined by the researchers that may affect the study For
T3 should exclude patiens with active autoimmune disease
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Ruijin hospital
Address:
City:
Shanghai
Zip:
200025
Country:
China
Status:
Recruiting
Contact:
Last name:
Mingci Cai, MD
Phone:
86-21-64370045
Phone ext:
665251
Investigator:
Last name:
Weili Zhao, MD
Email:
Principal Investigator
Investigator:
Last name:
Shu Cheng, MD
Email:
Sub-Investigator
Investigator:
Last name:
Mingci Cai, MD
Email:
Sub-Investigator
Investigator:
Last name:
Yaohui Huang, MD
Email:
Sub-Investigator
Start date:
February 13, 2023
Completion date:
July 15, 2028
Lead sponsor:
Agency:
Ruijin Hospital
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital of Nanchang University
Agency class:
Other
Collaborator:
Agency:
Peking University Third Hospital
Agency class:
Other
Collaborator:
Agency:
Wuhan TongJi Hospital
Agency class:
Other
Collaborator:
Agency:
West China Hospital
Agency class:
Other
Collaborator:
Agency:
Nanfang Hospital, Southern Medical University
Agency class:
Other
Collaborator:
Agency:
Anhui Provincial Cancer Hospital
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital of Soochow University
Agency class:
Other
Collaborator:
Agency:
The Second Affiliated Hospital of Harbin Medical University
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital of Xiamen University
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital of Zhengzhou University
Agency class:
Other
Collaborator:
Agency:
Beijing Tongren Hospital
Agency class:
Other
Collaborator:
Agency:
Peking University People's Hospital
Agency class:
Other
Collaborator:
Agency:
Sun Yat-sen University
Agency class:
Other
Collaborator:
Agency:
The First Affiliated Hospital of Anhui Medical University
Agency class:
Other
Collaborator:
Agency:
The First Hospital of Jilin University
Agency class:
Other
Source:
Ruijin Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05675813