Clinical trial NCT05675813: Genotype-guided Treatment in Newly Diagnosed PTCL
Official title: Guidance-04：T-cell Lymphoma Series：A Genotype-guided Therapy in Newly Diagnosed Patients With Peripheral T-cell Lymphoma （THEORY Study）
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Peripheral T Cell Lymphoma
Keywords: Biomarker-driven
Genetic subtypes
Complete response rate
Phase 1/2
Precision medicine
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Nanchang University
name: Peking University Third Hospital
name: Wuhan TongJi Hospital
name: West China Hospital
name: Nanfang Hospital, Southern Medical University
name: Anhui Provincial Cancer Hospital
name: The First Affiliated Hospital of Soochow University
name: The Second Affiliated Hospital of Harbin Medical University
name: The First Affiliated Hospital of Xiamen University
name: The First Affiliated Hospital of Zhengzhou University
name: Beijing Tongren Hospital
name: Peking University People's Hospital
name: Sun Yat-sen University
name: The First Affiliated Hospital of Anhui Medical University
name: The First Hospital of Jilin University
First posted: 2023-01-09
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D) for Phase I
timeFrame: DLT time window (28 days from Cycle 2)
measure: Complete response rate (CRR) for Phase II
timeFrame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days])
Secondary outcomes:
measure: Progression-free survival
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Overall survival
timeFrame: Baseline up to data cut-off (up to approximately 2 years)
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: From enrollment to study completion, a maximum of 4 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin hospital
state: Shanghai
Study officials:
References: