Genotype-guided Treatment in Newly Diagnosed PTCL

NCT05675813 | Recruiting Phase 1 DMC

• 1 other identifier: Guidance-04 (NHL-016)
• Study Type: interventional
• Target: 264
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Peripheral T Cell Lymphoma

Keywords

Biomarker-driven; Genetic subtypes; Complete response rate; Phase 1/2; Precision medicine

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 traditional "3+3" dose escalation methods

  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=21 days])

Secondary Outcomes (3)

• 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)

• 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 (3)

T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP

EXPERIMENTAL

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.

Drug: CHOP+selinexor+5-Azacitidine; Drug: standard CHOP

T2: CHOP+duvelisib+5-Azacitidine vs CHOP

EXPERIMENTAL

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.

Drug: CHOP+duvelisib+5-Azacitidine; Drug: standard CHOP

T3: CHOP+chidamide+tislelizumab （CHOPX2）vs CHOP

EXPERIMENTAL

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.

Drug: CHOP+chidamide+tislelizumab; Drug: standard CHOP

Interventions

CHOP+selinexor+5-Azacitidine DRUG

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.

T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP

CHOP+duvelisib+5-Azacitidine DRUG

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.

T2: CHOP+duvelisib+5-Azacitidine vs CHOP

CHOP+chidamide+tislelizumab DRUG

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.

T3: CHOP+chidamide+tislelizumab （CHOPX2）vs CHOP

standard 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 of every 21-day cycle for the 6 cycles.

T1: CHOP+selinexor+5-Azacitidine (CHOPX2) vs CHOP; T2: CHOP+duvelisib+5-Azacitidine vs CHOP; T3: CHOP+chidamide+tislelizumab （CHOPX2）vs CHOP

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
• 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

Sponsors & Collaborators

• Ruijin Hospital: lead
• The First Affiliated Hospital of Nanchang University: collaborator
• Peking University Third Hospital: collaborator
• Wuhan TongJi Hospital: collaborator
• West China Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Anhui Provincial Cancer Hospital: collaborator
• The First Affiliated Hospital of Soochow University: collaborator
• The Second Affiliated Hospital of Harbin Medical University: collaborator
• The First Affiliated Hospital of Xiamen University: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• Beijing Tongren Hospital: collaborator
• Peking University People's Hospital: collaborator
• Sun Yat-sen University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• The First Hospital of Jilin University: collaborator

Study Sites (1)

Ruijin hospital

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

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

Central Study Contacts

Weili Zhao

CONTACT

+862164370045; 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: December 29, 2022
• First Posted: January 9, 2023
• Study Start: February 13, 2023
• Primary Completion: July 15, 2026
• Study Completion (Estimated): July 15, 2028
• Last Updated: January 8, 2024

Record last verified: 2024-01

Locations

CN (1)