P2, N=90, Recruiting, Sun Yat-sen University

P3, N=560, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2028 --> Nov 2034

P2, N=240, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2025 --> Jul 2027

P1/2, N=43, Recruiting, Beijing Tongren Hospital

Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.

P2, N=210, Recruiting, Fudan University

P1, N=6, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting | N=24 --> 6

In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

P1, N=12, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | N=88 --> 12 | Trial completion date: Nov 2027 --> Nov 2024 | Trial primary completion date: Nov 2027 --> Nov 2024

P2/3, N=122, Recruiting, Institut de Recherches Internationales Servier | Trial completion date: Aug 2026 --> Feb 2027

P1, N=20, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1b --> P1 | Trial primary completion date: Sep 2027 --> Nov 2024

P1, N=19, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=62 --> 19

P3, N=440, Recruiting, Children's Oncology Group | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

One of the main limitations of the frontline pegaspargase (PEG) chemotherapy is the development of hypersensitivity reactions and subsequent development of anti-asparaginase neutralizing antibodies that lead to PEG inactivation...Instead of a single SNP association approach, identifying combinations of variations in pathway specific genes provides a more robust means to predict drug response. Our preliminary results provide a rationale for identification of genome level variations in this cohort and association analysis to establish clinically relevant pharmacogenomics score to optimize PEG treatment.

In this high-risk, heavily treated population, the combination of fludarabine, cytarabine, and PegC is feasible. Responding patients included 2 AML and 1 ALL. Further exploratory analysis about the relation between response and asparagine depletion as well as specific sensitive subsets could clarify which patients might benefit the most from this combination.

Recently, Xue et al showed that chidamide in combination with cisplatin, etoposide or gemcitabine showed synergistic effect and reversed the chemotherapy resistance in the relapsed/refractory B-cell lymphoma. This study demonstrates that sandwich CP-GEMOX chemoradiotherapy is a safe and promising approach to managing patients with early-stage ENKTL-NT.

Despite the introduction of asparaginase/pegaspargase-based chemotherapy, the prognosis of patients with advanced NKTCL needs to be improved, and few salvage treatment options are available for relapsed/refractory patients who fail chemotherapy...Immunotherapy has emerged and shown favorable antitumor activity in NKTCL, including monoclonal antibodies targeting immune checkpoint inhibitors, other receptors on the cellular membrane, and cellular immunotherapy, which could enhance immune cells attack on tumor cells. In this review, we provide an overview of recent immunotherapy in NKTCL, focusing on programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), chimeric antigen receptor (CAR) T cells, EBV-specific cytotoxic T lymphocytes, immunomodulatory agents, and other targeted agents, as well as the current progress and challenges in the field.

We reported in vitro and in vivo depletion of Gln induced by long-acting Erwinia asparaginase, PegC, inhibited proliferation of complex karyotype (CK) AML and synergistically enhanced the antiapoptotic activity of Ven-mediated antagonism of Bcl-2 by decreasing the expression of proteins such as Mcl-1, whose translation is cap-dependent...Pt 31 (post-alloHSCT relapsed AML with FLT3-ITD) who had persistent disease after gilteritinib achieved an MRD-negative CRi, pending 2nd alloHSCT... VenPegC is a novel regimen that can induce complete remission in some heavily pretreated R/R AML patients, even with previous exposure to Ven. Pts with RUNX1 mutation, whose translation depends on pheIF4E, may benefit further from this regimen.

The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.

P1, N=40, Recruiting, New York Medical College | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

An asparaginase product displaying the same characteristics of the Erwinia chrysanthemi asparaginase recently has been produced by use of recombinant technology, thus securing a preparation available for use as an alternative, or as a back-up in case of shortages, for the non-recombinant product. The long journey of the Erwinia chrysanthemi asparaginase product as it has developed throughout the last several decades has made it possible for almost every child and adult with ALL to complete the asparaginase-based protocol treatment when an immunological reaction has occurred to any Escherichia coli asparaginase product.

The incidence of serious clinical toxicities was low in this study, particularly pegaspargase-related venous thromboembolism. This suggests that the practice of capping pegaspargase doses at 3750 units, coupled with vigilant monitoring and prophylaxis for pegaspargase-related adverse events, can allow for the inclusion of this drug in the treatment of older individuals.

Based on the response rate and median disease-free period, treatment with pegylated-l-asparaginase is inferior when compared with historical chemotherapy protocols. However, some cats demonstrated an exceptional long disease-free period. Therefore, pegylated-l-asparaginase could be offered as an alternative to corticosteroid therapy alone. Further studies are needed to evaluate the additional benefit over palliative corticosteroid monotherapy.

P3, N=440, Recruiting, Children's Oncology Group | Not yet recruiting --> Recruiting

P1, N=12, Not yet recruiting, Porton Biopharma Limited

P1, N=27, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting

P3, N=440, Not yet recruiting, Children's Oncology Group | Initiation date: May 2023 --> Oct 2023

This pegarspargase-containing risk-oriented program was feasible and improved outcome of Ph- ALL/LL patients up to 65 years in a multicenter national setting. ClinicalTrials.gov #NCT02067143.

No abstract available

Bio-similar Pegaspargase in combination with chemotherapy was safe and tolerable in the pediatric ALL patients treated according to ICiCLe ALL-14 protocol. Suspected AEs ranged from mild to moderate and hepatic failure and hyperglycemia being severe.

They were treated with a DDGP regimen (cisplatin/dexamethasone/gemcitabine/pegaspargase), with the female patient evolving to death and the male patient showing a good response to chemotherapy. The prognosis of nasal NK/T-cell lymphoma is variable, with some patients responding well to therapy and others dying from disseminated disease despite aggressive therapy. As NK/T-cell lymphomas are uncommon even in regions where they are most prevalent, multicenter clinical trials are needed to adequately guide future treatments

In the present study, we compared a recombinant E. coli-derived ASNase marketed in Europe (Spectrila®) with an E. coli-derived ASNase preparation from India (Onconase) marketed in Eastern European countries. Our results reveal that Spectrila® met all of the testing parameters, stood out for its excellent quality and, thus, represents a safe treatment option in ALL. These findings are particularly important for low- and middle-income countries, where access to ASNase formulations is limited.

P2, N=50, Recruiting, Sun Yat-sen University | Unknown status --> Recruiting | Trial completion date: Mar 2021 --> Mar 2025 | Trial primary completion date: Mar 2021 --> Mar 2025

No treatment-related deaths occurred. First-line sintilimab, anlotinib, and pegaspargase sandwiched with radiotherapy demonstrated promising efficacy in treatment-naïve early-stage ENKTL patients with a favorable safety profile.

P1, N=62, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

No abstract available

Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

A total of 233 patients were included in this study, of which most patients were diagnosed with LBL, 120 (54%) patients were older than 14 years, and the male-to-female ratio was around 3:1. Overall, 170 patients received modified BFM-90 regimen, while the rest received modified BFM-95 regimen, both containing pegaspargase. Eventually, 195 (87.4%) patients achieved CR, the estimated 5-year PFS was 70.4% (95%CI: 64.2, 77.2), 5-year overall survival reached 75.5% (95% CI: 69.5, 82.1).

Background: With the application of pegaspargase (Asp) and early intervention with radiotherapy, the clinical outcome of extranodal NK/T cell lymphoma (ENKTL) has been improved significantly... This study suggests that ENKTL is accompanied by dyslipidemia. Baseline levels and change trends of TG and ApoA1 could contribute to risk stratification, disease status monitoring and treatment outcome prediction. Patients with dyslipidemia also have intratumoral lipid metabolic disorders and dysregulated classical tumor-related signaling pathway