Genotype-guided Targeted Agents Plus EZH2i for Primary Refractory PTCL

Official title

Genotype-guided Targeted Agents in Combination With EZH2 Inhibitor, Zeprumetostat for Primary Refractory Peripheral T-cell Lymphoma (PTCL), a Prospective, Open-label, Multi-center Study

Overview

To evaluate the safety and efficacy of Zeprumetostat-based combination therapy, selected according to genotyping results, in patients with primary refractory peripheral T-cell lymphoma (PTCL).

Detailed description

Peripheral T-cell lymphoma (PTCL) is a distinct and heterogeneous histopathologic subtype of non-Hodgkin lymphoma (NHL), accounting for \~10%. Patients with PTCL still have poor treatment response and prognosis under conventional CHOP regimen. Clinical outcomes of refractory patients are even poorer. Targeted drugs are warranted in this group of patients to improve survival. This prospective, multi-center, open-label study will evaluate the efficacy and safety of targeted drug in combination with Zeprumetostat, an EZH2 inhibitor in treatment of primary refractory peripheral peripheral T-cell lymphoma.

Interventions

• Drug Zeprumetostat+Azacitadine
  Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Azacitadine :100mg D1-D7, subcutaneous injection, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Azacitidine 100 mg D1-D5, subcutaneous injection for total 3 cycles.
• Drug Zeprumetostat+Decitabine
  Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Decitabine 10mg/m2 D1-D5, intravenous infusion, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Decitabine 10mg/m2 D1-D3 for total 3 cycles.
• Drug Zeprumetostat+Chidamide
  Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Chidamide 30 mg biw orally, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Chidamide 20 mg biw for total 3 cycles.
• Drug Zeprumetostat+Golidocitinib
  Zeprumetostat: 350 mg bid, orally, till disease progression (PD) or unacceptable toxicity. Golidocitinib 150 mg qd orally, should ≥2 out of 6 pts experience a DLT, the dose will be adjusted to: Golidocitinib 150 mg qod for total 3 cycles.

Primary outcome measures

• Summary of DLT events (Phase Ib) [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Overall response rate (Phase Ⅱ) [Time frame: At the end of Cycle 3 (each cycle is 28 days)]

Secondary outcome measures (8)

• Complete response rate [Time frame: At the end of Cycle 3]
• Disease Control Rate [Time frame: each cycle is 28 days]
• Duration of response [Time frame: Baseline up to data cut-off]
• Duration of complete response [Time frame: Baseline up to data cut-off]
• Progression free survival [Time frame: Baseline up to data cut-off]
• Overall survival [Time frame: Baseline up to data cut-off]
• Treatment-Related Adverse Events [Time frame: Baseline up to data cut-off]
• Exploratory biomarker analysis [Time frame: Baseline up to data cut-off]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years, male or female.
• Patients with a histopathologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) based on 2016 WHO classification
• Previously treated with 3 or 6 cycles of a CHOP-like regimen as first-line therapy and considered primary refractory. Patients with anaplastic large cell lymphoma (ALCL) must have adequately received brentuximab vedotin (BV) as part of their first-line treatment.
• Tumor tissue genotyping performed and results available prior to enrollment.
• ECOG 0, 1, or 2.
• Life expectancy greater than 3 months.
• Adequate organ function
• Contraception during study
• Informed consented

Exclusion criteria

• Has a prior malignancy other than the malignancies under study within 3 years without relieve
• Primary CNS lymphoma
• Known hypersensitivity to any study drug.
• Pregnant or lactation
• Active infection.
• Diseases and medical history:

• Requires continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers
• Has multiple factors affecting oral medication administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
• Has a history of psychoactive substance abuse that cannot be discontinued
• Has any severe and/or uncontrolled disease.
• Uncontrollable autoimmune disease,
• Not able to comply to the protocol for mental or other unknown reasons
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07493330 · Target

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗