In decades, the outcome of patients with peripherial T-cell lymphomas is dismal, especially in relapsed or refractory population. After failure to the frontline treatment, patients have limited treatment options and elderly population usually have no chance to undergo transplantation due to age or comorbidity, etc. EZH2 inhibitor like Tazemetostat or SHR 2554 has been demonstrated its anti-tumor activity in PTCL either alone or in combination with other targeted agents. This study aims to explore the efficacy and safety of Tazemetostat in combination with Linperlisib/Golidocitinib in Patients With Relapsed/Refractory Peripheral T-cell Lymphoma in the patients with peripheral T-cell lymphoma according to next-generation sequesing results.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Tazemetostat 800mg, twice once daily (BID), orally
In Phase I, BOIN design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of Linperlisib: 60 mg once daily (QD) and 60 mg QD, orally. In Phase II, BOP2 design will be adopted to enroll around 24 participants, aiming to evaluate the efficacy and safety of Tazemetostat with Linperlisib RP2D in patients with peripheral T-cell lymphoma with co-RHOA/TET2mut.
In Phase I, BOIN design will be adopted to enroll 3 to 12 participants, exploring the recommended Phase II dose (RP2D) at two dose levels of Lgolidocitinib: 150 mg every other day (QOD) and 150 mg QD, orally. In Phase II, BOP2 design will be adopted to enroll around 24 participants, aiming to evaluate the efficacy and safety of Tazemetostat with Golidocitinib RP2D in patients with peripheral T-cell lymphoma without co-RHOA/TET2mut.
Overall Response Rate
Percentage of participants with complete response or partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria
Time frame: Tumor evaluation was assessed at screening and at the end of treatment (around 3 cycles) then every 12-24 weeks until disease progression (each cycle is 28 days) through study completion, an average of 1 year.
Progression-free survival
Progression-free survival was defined as the time from the date of enrollment 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.
Time frame: Baseline up to data cut-off(up to approximately 2 years).
Complete Response Rate
Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.
Time frame: Tumor evaluation was assessed at screening and at the end of treatment (around 3 cycles) then every 12-24 weeks until disease progression (each cycle is 21 days) through study completion, an average of 1 year.
Duration of Response
Applicable to complete or partial response participants. DoR was defined as the time from the first documented date of complete or partial response until the date of the disease progression or death from any causes.
Time frame: Baseline up to data cut-off(up to approximately 2 years).
Overall survival
Overall survival was defined as the time from the date of enrollment to the date of death from any cause.
Time frame: Baseline up to data cut-off(up to approximately 3 years).
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
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.
Time frame: From enrollment to study completion, a maximum of 2 years]
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