PTCL-NOS
Conditions
Brief summary
This is a single-arm, multi-cohort, multicenter, phase Ib/IIa clinical study designed to evaluate the safety and efficacy of Zeprumetostat (an EZH2 inhibitor) in combination with different therapeutic agents/regimens - specifically, the JAK1 inhibitor golidocitinib and the GemOx chemotherapy regimen (gemcitabine plus oxaliplatin) - in patients with relapsed or refractory peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and T-follicular helper cell lymphoma (TFHL). The trial comprises a phase Ib dose-escalation phase and a phase IIa dose-expansion phase. Two combination cohorts are established: Cohort A (zemitostatin + golidocitinib) and Cohort B (zemitostatin + GemOx). Subjects will be randomly assigned to either Cohort A or Cohort B.
Interventions
DRUGZeprumetostat( an EZH2 inhibitor) + X
Zeprumetostat( an EZH2 inhibitor) + JAK1 inhibitor or GemOx
Sponsors
Tianjin Medical University Cancer Institute and Hospital
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
1. Age 18 years or older, both males and females are eligible; 2. Histologically confirmed peripheral T-cell lymphoma (PTCL) including PTCL-NOS and TFHL that has relapsed or is refractory after at least one line of systemic therapy. The definitions are as follows: Relapse: Patients who achieved a Complete Response (CR) in previous treatments and have new lesions at the original site or elsewhere; Refractory: Patients who did not achieve CR after adequate treatment. For nasal-type NK/T-cell lymphoma, previous treatments must have included a chemotherapy regimen containing asparaginase; 3. Patients who have undergone prior hematopoietic stem cell transplantation are allowed; 4. ECOG PS 0-2 5. Life expectancy greater than 3 months. 6. Adequate organ function 7. Contraception during study 8. Informed consented
Exclusion criteria
1. Prior treatment with EZH2 inhibitors or EZH1/2 inhibitors before enrollment; 2. Peripheral T-cell lymphoma of subtypes other than PTCL-NOS and TFHL; 3. History of other primary invasive malignancies that have not been in remission or have been in remission for no more than 3 years; 4. Central nervous system involvement (meningeal or parenchymal); 5. Known hypersensitivity to any study drugs; 6. Participation in another clinical trial of an investigational drug within 4 weeks prior to the start of the study. 7. Pregnant or lactation 8. Active infection. 9. 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. 10. Uncontrollable autoimmune disease, 11. Not able to comply to the protocol for mental or other unknown reasons 12. 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 21 days) | A Phase Ib Dose-Finding Study of Zeprumetostat in Combination Using a 3+3 Design |
| Overall response rate (Phase Ⅱ) | Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1) | Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment EZH2+JAK1/GeMox |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1) | Complete Response Rate (CRR) is defined as the proportion of subjects who achieve CR after treatment EZH2+JAK1/GeMox |
| Duration of response | Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1) | Duration of Remission (DoR) is defined as the time from the first documentation of remission (CR or PR) to the first documented relapse evidence of the responders. |
| Progression free survival | Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1) | 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 | Through study completion, an average of 3 years after EZH2+JAK1/GemOx (Day 1) | 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 |
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE | Through study completion, an average of 2 years after EZH2+JAK1/GemOx (Day 1) | 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 |
Countries
China
Contacts
CONTACTZhang huilai, MD
Outcome results
None listed