PTCL, Refractory
Conditions
Keywords
PTCL, Genotype-guided, Zeprumetostat, Refractory
Brief summary
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
DRUGZeprumetostat+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.
DRUGZeprumetostat+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.
DRUGZeprumetostat+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.
DRUGZeprumetostat+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.
Sponsors
Ruijin Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Requires continuous treatment with strong or moderate CYP3A inhibitors or CYP3A inducers 2. Has multiple factors affecting oral medication administration (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.); 3. Has a history of psychoactive substance abuse that cannot be discontinued 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of DLT events (Phase Ib) | At the end of Cycle 1 (each cycle is 28 days) | Measure Description: Enroll 6 pts per cohort and observe the number of pts experiencing dose-limiting toxicity. |
| Overall response rate (Phase Ⅱ) | At the end of Cycle 3 (each cycle is 28 days) | Percentage of participants with overall response was determined on the basis of investigator assessments according to 2014 Lugano criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | At the end of Cycle 3 | Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria |
| Disease Control Rate | each cycle is 28 days | 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 |
| Duration of response | Baseline up to data cut-off | 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. |
| Duration of complete response | Baseline up to data cut-off | 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. |
| Progression free survival | Baseline up to data cut-off | 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. |
| Overall survival | Baseline up to data cut-off | 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. |
| Treatment-Related Adverse Events | Baseline up to data cut-off | 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. |
| Exploratory biomarker analysis | Baseline up to data cut-off | Exploratory biomarker to predict treatment response and survival |
Contacts
CONTACTWeili Zhao
CONTACTPengpeng Xu
Outcome results
None listed