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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zeprumetostat+Azacitadine (if with TET2 plus RHOA gene mutation) | Experimental | 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. |
|
| Zeprumetostat+Decitabine (if with TP53 gene mutation) | Experimental | 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. |
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| Zeprumetostat+Chidamide (if with CREBBP/EP300/KMT2C/KMT2D/NCOR2 gene mutation) | Experimental | 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. |
|
| Zeprumetostat+Golidocitinib (if not above genotype) | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zeprumetostat+Azacitadine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Summary of DLT events (Phase Ib) | Measure Description: Enroll 6 pts per cohort and observe the number of pts experiencing dose-limiting toxicity. | At the end of Cycle 1 (each cycle is 28 days) |
| Overall response rate (Phase Ⅱ) | Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria | At the end of Cycle 3 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Complete response rate | Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria | At the end of Cycle 3 |
| Disease Control Rate |
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Inclusion Criteria:
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:
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weili Zhao | Contact | 086-022-64370045 | zwl_trial@163.com | |
| Pengpeng Xu | Contact | pengpeng_xu@126.com |
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| Zeprumetostat+Decitabine | Drug | 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. |
|
| Zeprumetostat+Chidamide | Drug | 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. |
|
| Zeprumetostat+Golidocitinib | Drug | 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. |
|
Percentage of participants with complete response, partial response, or stable disease, as determined by investigator assessment according to the 2014 Lugano criteria, at the end of Cycle 3
| each cycle is 28 days |
| Duration of response | Time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT. | Baseline up to data cut-off |
| Duration of complete response | Time from first occurrence of documented CR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with PET-CT. | Baseline up to data cut-off |
| Progression free survival | Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first. | Baseline up to data cut-off |
| Overall survival | Overall survival was defined as the time from the date of diagnosis to the date of death from any cause. Reported is the percentage of participants with event. of disease progression or relapse, using 2014 Lugano criteria,or death from any cause, whichever occurred first. | Baseline up to data cut-off |
| Treatment-Related Adverse Events | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Baseline up to data cut-off |
| Exploratory biomarker analysis | Exploratory biomarker to predict treatment response and survival | Baseline up to data cut-off |