Clinical trial NCT06376721: Linperlisib Combined With Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-cell Lymphoma
Official title: A Phase Ib/II Clinical Trial of Linperlisib Combined With Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
T-lymphoblastic Lymphoma
Keywords: r/r ENKTL
Linperlisib
PD-1 blockade
Pegaspargase
Lead sponsor: Beijing Tongren Hospital
Sponsor class: OTHER
First posted: 2024-04-19
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Treatment with linperlisib in combination with camrelizumab and pegaspargase for advanced or relapsed/refractory ENKTCL patients
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The best objective response rate（ORR） over 6 treatment cycles
timeFrame: Within 6 treatment cycles (each cycle is 21 days)
Secondary outcomes:
measure: Objective Response Rate（ORR）
timeFrame: At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days)
measure: Complete Response （CR）
timeFrame: At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days)
measure: Progression Free Survival (PFS)
timeFrame: From date of enrollment until the date of progression or date of death from any cause, whichever came first, assesed up to 2 years.
measure: Overall Survival (OS)
timeFrame: From date of enrollment until the date of documented death from any cause or follow up, whichever came first, assesed up to 2 years.
measure: Disease Control Rate（DCR）
timeFrame: Up to 2 years after enrollment.
Other outcomes:
measure: Drug safety
timeFrame: up to 2 years after enrollment
Locations:
city: Beijing
country: China
facility: Liang Wang
state: Beijing
Study officials:
affiliation: Beijing Tongren Hospital
name: Liang Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: