A New Genotype-guided Therapy in Newly Diagnosed Patients With Peripheral T-cell Lymphoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Ruijin Hospital
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- Recommended Phase 2 Dose (RP2D) for Phase I
Study Overview
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.
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 and Guidance-04 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 targeted agents will be confirmed. In phase II, patients will receive standard CHOP for the first cycle and then 1:1 be randomized to CHOPX2 or CHOP regimen in four genetic subtypes.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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, 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
Outcomes
Primary Outcomes
Recommended Phase 2 Dose (RP2D) for Phase I
Time Frame: Dose Limiting Toxicity (DLT) time window (28 days from Cycle 2)
: Recommended Phase 2 Dose (RP2D) for Phase I of oral targeted agents in each genetic subtypes by BOIN methods
Complete response rate (CRR) for Phase II
Time Frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=28 days])
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Secondary Outcomes
- 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)
Investigators
Zhao Weili
Vice President, Ruijin Hospital
Ruijin Hospital