Linperlisib Combined With Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-cell Lymphoma

T-lymphoblastic Lymphoma Clinical Trial

Official title:

A Phase Ib/II Clinical Trial of Linperlisib Combined With Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-cell Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06376721
• Other study ID #: TREC2024-KY016
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 14, 2024
• Est. completion date: October 31, 2027

Study information

• Verified date: April 2024
• Source: Beijing Tongren Hospital
• Contact: Liang Wang, M.D.
• Phone: +861058268442
• Email: wangliangtrhos[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 43
• Est. completion date: October 31, 2027
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• T-lymphoblastic Lymphoma

Intervention

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

Locations

Country	Name	City	State
China	Liang Wang	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tongren Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Drug safety	According to NCI CTCAE v5.0	up to 2 years after enrollment
Primary	The best objective response rate(ORR) over 6 treatment cycles	Overall response rate means sum of complete response rate and partial response rate	Within 6 treatment cycles (each cycle is 21 days)
Secondary	Objective Response Rate(ORR)	Objective response rate means sum of complete response rate and partial response rate	At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days)
Secondary	Complete Response (CR)	CR was defined as complete remission evaluated using PET-CT scan or BM test	At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days)
Secondary	Progression Free Survival (PFS)	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.	From date of enrollment until the date of progression or date of death from any cause, whichever came first, assesed up to 2 years.
Secondary	Overall Survival (OS)	Overall survival is defined as the time from the date of treatment to the date of death.	From date of enrollment until the date of documented death from any cause or follow up, whichever came first, assesed up to 2 years.
Secondary	Disease Control Rate(DCR)	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	Up to 2 years after enrollment.