Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type, T-lymphoblastic Lymphoma
Conditions
Keywords
r/r ENKTL, Linperlisib, PD-1 blockade, Pegaspargase
Brief summary
The patients diagnosed with relapsed/refractory or advanced NK/T-cell Lymphoma (r/r NKTCL) were selected as the research objects. To explore effective and safe treatment for advanced or r/r NKTCL, the combination of PI3K-δ inhibitor Linperlisib with PD-1 blockade Camrelizumab and anti-metabolic agent Pegaspargase was applied for the treatment.
Detailed description
This is a prospective, single-arm, single-center Ib/II clinical trial that included an initial safety run-in phase with safety monitoring before the main enrollment (expansion phase).The aim of phase Ib is to evaluate the recommended phase 2 dose and dose-limiting toxicity (DLT), and the aim of phase II study is to evaluate, for the first time, the safety and efficacy of the treatment of Linperlisib combined with PD-1 blockade Camrelizumab and Pegaspargase in patients diagnosed with advanced or r/r ENKTL, respectively.
Interventions
DRUGLinperlisib
Linperlisib: Phase Ib, oral, 80 mg/d, QD; Phase II, oral, RP2D, QD.
DRUGCamrelizumab
Camrelizumab for Injection: 200 mg/d, intravenous drip for 30 min (not less than 20 min and not more than 60 min), administered on day 1 of each cycle, observed for 2 hours after infusion. Every 3 weeks is a dosing cycle. Cycle 2 and subsequent cycles of dosing may be administered up to 5 days before or after the day of the scheduled dosing; more than 3 days after the date of the scheduled dosing will be considered a delayed dosing.
DRUGPegaspargase
Pegaspargase: 2500 IU/m2, intramuscular injection, divided into three places, administered on the first day of each cycle, observed 2 hours after injection for the occurrence of anaphylactic reaction, if there is no anaphylactic reaction before giving other test drugs. Every 3 weeks as a dosing cycle. Camrelizumab for Injection should not be applied on the same day as Dexamethasonee.
DRUGDexamethasone
Dexamethasone, 20 mg/d, days 1-4. Camrelizumab for Injection should not be applied on the same day as Dexamethasonee.
Sponsors
Beijing Tongren Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment with linperlisib in combination with camrelizumab and pegaspargase for advanced or relapsed/refractory ENKTCL patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histopathology and immunohistochemistry confirmed diagnosis of ENKTL according to WHO 2016 criteria. * refractory or relapsed after initial remission, or Ann-Arbor stage III-IV de novo patients * PET/CT or CT/MRI with at least one objectively evaluable lesion. * Expected to survive more than 3 months. * General status ECOG score 0-2 points. * The laboratory test within 1 week before enrollment meets the following conditions: Blood routine: WBC≥3×10e9/L, PLT≥75×10e9/L, ANC≥1.5×10e9/L. sCR≤1.5 mg/dL,GFR≥50 ml/min. Liver function: ALT & AST≤3 times the upper limit of normal, TBIL ≤2 times the upper limit of normal. Serum fibrinogen level≥1.0 g/L. •Sign the informed consent form
Exclusion criteria
* Patients with CNS involvement, or with other neoplasm; * Patients has received PI3K inhibitor treatment before enrollment * Poor performance status, ECOG≥2; * Patients in lactation or pregnancy； * Patients (male or female) have the possibility of childbirth but are unwilling or have not taken effective contraceptive measures； * Patients allergic to any of the study drugs； * Patients with active infection； * Patients with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; * Patients with a history of interstitial pneumonia, non infectious pneumonia, or highly suspected interstitial pneumonia; * Patients with a history of neurological or psychiatric disorders, including epilepsy or dementia, in the past * According to the researcher's judgment, there are accompanying diseases that seriously endanger patient safety or affect patient completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The best objective response rate（ORR） over 6 treatment cycles | Within 6 treatment cycles (each cycle is 21 days) | Overall response rate means sum of complete response rate and partial response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response （CR） | At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days) | CR was defined as complete remission evaluated using PET-CT scan or BM test |
| Objective Response Rate（ORR） | At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days) | Objective response rate means sum of complete response rate and partial response rate |
| Overall Survival (OS) | From date of enrollment until the date of documented death from any cause or follow up, whichever came first, assesed up to 2 years. | Overall survival is defined as the time from the date of treatment to the date of death. |
| Disease Control Rate（DCR） | Up to 2 years after enrollment. | Disease control rate discribes the percentage of patients with advanced cancer whose therapeutic intervention has led to a complete response, partial response, or stable disease |
| Progression Free Survival (PFS) | From date of enrollment until the date of progression or date of death from any cause, whichever came first, assesed up to 2 years. | Progression free survival was defined as the period from the start of treatment to the date of confirmed disease progression or death from any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Drug safety | up to 2 years after enrollment | According to NCI CTCAE v5.0 |
Countries
China
Contacts
Primary ContactLiang Wang, M.D.
Outcome results
None listed