New Genotype-guided Treatment in Newly Diagnosed PTCL

NCT07706959 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: Guidance-08
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I/II study evaluate the safety and efficacy targeted agents in combination with standard CHOP in new genotypic subtypes in treatment naive peripheral T-cell lymphoma. Phase I is to confirm RP2D of targeted agent. Phase II is a multicenter, prospective, randomized, open-label, controlled design to evaluate the efficacy and safety of new 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.

Conditions

Peripheral T-cell Lymphoma (PTCL)

Keywords

Biomarker-driven; Genetic subtypes; Precision medicine; Peripheral T Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) for Phase I

  : Recommended Phase 2 Dose (RP2D) for Phase I of oral targeted agents in each genetic subtypes by BOIN methods

  Dose Limiting Toxicity (DLT) time window (28 days from Cycle 2)

• Complete response rate (CRR) for Phase II

  Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days])

Secondary Outcomes (4)

• Progression-free survival

  Baseline up to data cut-off (up to approximately 2 years)

• Overall survival

  Baseline up to data cut-off (up to approximately 2 years)

• Overall response rate (ORR)

  End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days])

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  From enrollment to study completion, a maximum of 4 years

Study Arms (4)

Subgroup 1

EXPERIMENTAL

TET2/RHOA co-mutated genetic subtype

Drug: Azacitidine plus Selinexor with CHOP; Drug: CHOP

Subgroup 2

EXPERIMENTAL

TP53-mutated genetic subtype

Drug: Decitabine plus Selinexor with CHOP; Drug: CHOP

Subgroup 3

EXPERIMENTAL

Core epigenetic genes-mutated genetic subtype

Drug: Zeprumetostat plus chidamide with CHOP; Drug: CHOP

Subgroup 4

EXPERIMENTAL

Other genetic subtype

Drug: Azacitidine plus Golidocitinib with CHOP; Drug: CHOP

Interventions

Azacitidine plus Selinexor with CHOP DRUG

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 for the first cycle. If tumor NGS indicates TP53-mutated genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive azacitidine d-5 to d-1 and Selinexor 40mg qw combined with standard CHOP.

Subgroup 1

Decitabine plus Selinexor with CHOP DRUG

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 for the first cycle. If tumor NGS indicates TP53-mutated genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive Decitabine RP2D (confrimed by phase I) and Selinexor 40mg qw combined with standard CHOP.

Subgroup 2

Zeprumetostat plus chidamide with CHOP DRUG

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 for the first cycle. If tumor NGS indicates core epigenetic genes-mutated genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive Zeprumetostat RP2D (confrimed by phase I) and chidamide 20mg biw combined with standard CHOP.

Subgroup 3

Azacitidine plus Golidocitinib with CHOP DRUG

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 for the first cycle. If tumor NGS indicates other genetic subtype, then 1:1 randomized to experimental (CHOPX2) or standard CHOP regimen for 5 cycles of every 28-day cycle. Patients in CHOPX2 group will receive Azacitidine ih d-5-d-1 and Golidocitinib RP2D (confirmed by Phase I) combined with standard CHOP.

Subgroup 4

CHOP DRUG

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 for cycle 1 to cycle 6.

Subgroup 1; Subgroup 2; Subgroup 3; Subgroup 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients with ALCL and cutaneous TCL, MEITL, HSTCL, T-PLL, etc.
• 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\<1.5×10\^9/L Platelets\<75×10\^9/L (Neutrophils\<1.0×10\^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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

Azacitidine; selinexor; Decitabine; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Weili Zhao Zhao

CONTACT

+862164370045 Ext. 610707; zwl_trial@163.com

Pengpeng Xu

CONTACT

+862164370045; pengpeng_xu@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President, Ruijin Hospital

Study Record Dates

• First Submitted: July 11, 2026
• First Posted: July 16, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: July 16, 2026

Record last verified: 2026-07

Locations

CN (1)