Mature T-cell and NK-cell Lymphoma
Conditions
Brief summary
This is a prospective, multicenter, open-label, phase Ib/II clinical study to evaluate the safety and efficacy of EZH2 inhibitor Zeprumetostat in combination therapy for patients with relapsed or refractory mature T-cell and NK-cell lymphomas.
Interventions
DRUGZeprumetostat
350mg, po, bid
DRUGGolidocitinib
Cohort 1: Golidocitinib: 150mg, po, qd
DRUGChidamide
Cohort 2: Chidamide: 20mg, po, biw
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntarily participate in the clinical study; fully understand and be informed about the study and sign the Informed Consent Form (ICF); willing to comply with and capable of completing all trial procedures; * Age ≥ 18 years * Pathologically confirmed mature T-cell and NK-cell lymphomas. * Using the Lugano 2014 criteria, the patient must have at least one measurable or evaluable lesion * Participants must have experienced disease progression, treatment failure, or intolerance following standard therapy. Patients with ALCL are required to have previously received anti-CD30-targeted therapy, while patients with NKTCL must have previously been treated with pegaspargase or L-asparaginase. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Adequate organ and bone marrow function
Exclusion criteria
* Lymphoma involvement in the central nervous system or meninges * Active infections * Prior treatment with an EZH2 inhibitor or an EZH1/2 dual inhibitor that was discontinued due to intolerance to toxicity; * For patients enrolled in Cohort 1, prior treatment with a JAK inhibitor that was discontinued due to intolerance to toxicity; * For patients enrolled in Cohort 2, prior treatment with an HDAC inhibitor that was discontinued due to intolerance to toxicity. * History of Human Immunodeficiency Virus (HIV) infection and/or Acquired Immunodeficiency Syndrome (AIDS). * Patients with mental disorders or those unable to provide informed consent * Any other condition deemed by the investigator to be unsuitable for study enrollment; * Pregnant or breastfeeding women, and subjects of childbearing potential who are unwilling to use contraception; * Individuals with a known hypersensitivity to any of the investigational drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT for Phase 1b | The first cycle after administration (each cycle is 28 days) | To identify the dose-limiting toxicity |
| Overall response rate(ORR) for Phase 2 | Up to 24 months | The proportion of patients who achieve complete remission (CR) or partial remission (PR) as the best response. |
| RP2D for phase Ib | The first cycle after administration (each cycle is 28 days) | To identify the recommended phase 2 dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | Up to 24 months | Defined as the proportion of patients who achieve complete remission as the best response |
| Overall survival(OS) | Up to 4 years | To investigate the preliminary anti-tumor efficacy |
| Duration of Response(DOR) | Up to 4 years | To investigate the preliminary anti-tumor efficacy |
| Progression-free survival(PFS) | Up to 4 years | To investigate the preliminary anti-tumor efficacy |
Contacts
Primary ContactQingqing Cai, MD. PhD.
Outcome results
None listed