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

Overview

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

• Drug Linperlisib
  Linperlisib: Phase Ib, oral, 80 mg/d, QD; Phase II, oral, RP2D, QD.
• Drug Camrelizumab
  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.
• Drug Pegaspargase
  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.
• Drug Dexamethasone
  Dexamethasone, 20 mg/d, days 1-4. Camrelizumab for Injection should not be applied on the same day as Dexamethasonee.

Primary outcome measures

• The best objective response rate（ORR） over 6 treatment cycles [Time frame: Within 6 treatment cycles (each cycle is 21 days)]

Secondary outcome measures (5)

• Objective Response Rate（ORR） [Time frame: At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days)]
• Complete Response （CR） [Time frame: At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days)]
• Progression Free Survival (PFS) [Time frame: From date of enrollment until the date of progression or date of death from any cause, whichever came first, assesed up to 2 years.]
• Overall Survival (OS) [Time frame: From date of enrollment until the date of documented death from any cause or follow up, whichever came first, assesed up to 2 years.]
• Disease Control Rate（DCR） [Time frame: Up to 2 years after enrollment.]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Liang Wang — Beijing

Identifiers

NCT: NCT06376721 · TREC2024-KY016

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗