Combination of Mitoxantrone Liposome and Etoposide, Dexamethasone, Pegaspargase and Golidocitinib (MEPL-G) in the Treatment of NK/T-cell Lymphoma Associated Hemophagocytic Lymphohistiocytosis (NKTCL-HLH)

Summary

Extranodal NK/T-cell lymphoma (NKTCL) is an aggressive EBV-associated lymphoma with poor prognosis, highly prevalent in China. Early-stage NKTCL achieves favorable long-term survival, while advanced disease shows dismal outcomes with no standard therapy. Notably, 10%-20% of patients develop secondary hemophagocytic lymphohistiocytosis (NKTCL-HLH), a life-threatening complication with median survival \<2 months and mortality over 90%. Current treatments fail to simultaneously control lymphoma and hyperinflammation, with poor tolerance and high resistance. The JAK/STAT pathway drives EBV-induced inflammation and tumor progression. Golidocitinib, a selective JAK1 inhibitor, demonstrates potent anti-NKTCL activity and rapid inflammation control. Liposomal mitoxantrone offers targeted efficacy with lower toxicity, while etoposide, methylprednisolone, and pegaspargase provide synergistic anti-tumor and anti-HLH effects. This study proposes the novel MEPL-G regimen (liposomal mitoxantrone, etoposide, methylprednisolone, pegaspargase, golidocitinib) for NKTCL-HLH. By targeting both HLH and NKTCL, this combination aims to achieve rapid disease control, improve tolerance, and prolong survival, addressing the unmet critical clinical need for this high-risk population.

Eligibility

Inclusion Criteria:

* Histologically confirmed extranodal NK/T-cell lymphoma.
* Meeting the HLH-2004 diagnostic criteria (≥ 5 criteria).
* Age ≥ 18 years, regardless of gender.
* Negative HIV antigen or antibody.
* Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac echocardiography.
* No active visceral bleeding (e.g., gastrointestinal, pulmonary, cerebral).
* No uncontrolled infection (e.g., pulmonary infection, intestinal infection).
* Negative HCV antibody; or positive HCV antibody with negative HCV RNA.
* Negative HBsAg and negative HBcAb. If either is positive, peripheral blood HBV DNA load must be \< 1×10³ copies/mL to be eligible.
* Signed written informed consent and ability to understand and comply with all study requirements.

Exclusion Criteria:

* New York Heart Association (NYHA) cardiac function class ≥ II;
* Female patients who are pregnant or breastfeeding;
* Known hypersensitivity to any of the study drugs;
* Presence of other concurrent malignancies (except non-melanoma skin cancer);
* Concurrent central nervous system lymphoma infiltration;
* Severe psychiatric disorders or inability to comply with follow-up;
* Severe renal dysfunction (glomerular filtration rate \< 15 mL/min);
* Severe liver cirrhosis (MELD score \> 20);
* History of acute or chronic pancreatitis;
* Simultaneous participation in another clinical trial.

Conditions3

Interventions5

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