THEORY: Genotype-guided Treatment in PTCL

Sponsor

Ruijin Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05675813

Collaborator

Peking University People's Hospital (Other), Sun Yat-sen University (Other), Tongji Hospital (Other), West China Hospital (Other), Nanfang Hospital of Southern Medical University (Other)

264

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral T Cell Lymphoma	Drug: CHOP+selinexor+5-Azacitidine Drug: CHOP+duvelisib+5-Azacitidine Drug: CHOP+chidamide+tislelizumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

264 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

T-cell Lymphoma Series：A Genotype-guided Therapy in Newly Diagnosed Patients With Peripheral T-cell Lymphoma （THEORY Study）

Anticipated Study Start Date :

Jan 15, 2023

Anticipated Primary Completion Date :

Dec 15, 2024

Anticipated Study Completion Date :

Dec 15, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CHOP+selinexor+5-Azacitidine 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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and selinexor 40mg or 60mg in phase I triaI on days d1,d8 while selinexor RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.	Drug: CHOP+selinexor+5-Azacitidine 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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and selinexor 40mg or 60mg in phase I triaI on days d1,d8 while selinexor RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.
Experimental: CHOP+duvelisib+5-Azacitidine 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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg in phase I triaI on days d1-21 while duvelisib RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.	Drug: CHOP+duvelisib+5-Azacitidine 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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg in phase I triaI on days d1-21 while duvelisib RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.
Experimental: CHOP+chidamide+tislelizumab 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. For the remaining 5 cycles, they will receive tislelizumab 200mg d1 ivgtt and chidamide 20mg or 30mg po in phase I triaI biw while chidamide RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.	Drug: CHOP+chidamide+tislelizumab 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. For the remaining 5 cycles, they will receive tislelizumab 200mg d1 ivgtt and chidamide 20mg or 30mg po in phase I triaI biw while chidamide RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.

Arm

Intervention/Treatment

Experimental: CHOP+selinexor+5-Azacitidine

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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and selinexor 40mg or 60mg in phase I triaI on days d1,d8 while selinexor RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.

Drug: CHOP+selinexor+5-Azacitidine

Experimental: CHOP+duvelisib+5-Azacitidine

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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg in phase I triaI on days d1-21 while duvelisib RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.

Drug: CHOP+duvelisib+5-Azacitidine

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. For the remaining 5 cycles, they will receive 5-Azacitidine ih d-7-d-1 and duvelisib 25mg or 50mg in phase I triaI on days d1-21 while duvelisib RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.

Experimental: CHOP+chidamide+tislelizumab

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. For the remaining 5 cycles, they will receive tislelizumab 200mg d1 ivgtt and chidamide 20mg or 30mg po in phase I triaI biw while chidamide RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.

Drug: CHOP+chidamide+tislelizumab

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. For the remaining 5 cycles, they will receive tislelizumab 200mg d1 ivgtt and chidamide 20mg or 30mg po in phase I triaI biw while chidamide RP2D po in phase II trial followed by standard CHOP of every 21-day cycle.

Outcome Measures

Primary Outcome Measures

complete response rate [End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]]
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.

Secondary Outcome Measures

Progression-free survival [Baseline up to data cut-off (up to approximately 2 years)]
Progression-free survival was defined as the time from the date of randomization until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.
Overall survival [Baseline up to data cut-off (up to approximately 2 years)]
Overall survival was defined as the time from the date of randomization to the date of death from any cause.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 [From enrollment to study completion, a maximum of 4 years]
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically-confirmed Peripheral T-cell lymphoma
Availability of archival or freshly collected tumor tissue before study enrollment
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 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Ruijin Hospital
Peking University People's Hospital
Sun Yat-sen University
Tongji Hospital
West China Hospital
Nanfang Hospital of Southern Medical University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zhao Weili, Vice President, Ruijin Hospital, Ruijin Hospital

ClinicalTrials.gov Identifier:

NCT05675813

Other Study ID Numbers:

NHL-016

First Posted:

Jan 9, 2023

Last Update Posted:

Jan 9, 2023

Last Verified:

Dec 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Azacitidine

Study Results

No Results Posted as of Jan 9, 2023