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)

April 7, 2026 updated by: LIANG WANG, Beijing Tongren Hospital

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): a Prospective, Multi-center, Single Arm, Phase Ib/II Clinical Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Extranodal NK/T-cell lymphoma (NKTCL) is an aggressive Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma with particularly high incidence in Asia, especially in southern China where it accounts for 10%-15% of all malignant lymphomas. Early-stage NKTCL can achieve an 80% long-term survival rate with radiotherapy combined with pegaspargase-based chemotherapy. However, advanced and relapsed/refractory NKTCL carries a dismal prognosis, with long-term survival below 40%. A severe complication is hemophagocytic lymphohistiocytosis (HLH), which develops in 10%-20% of patients and leads to an extremely aggressive clinical course, with median survival less than 2 months and 6-month overall survival of only 23%.

Pathogenically, EBV infection induces abnormal immune activation through the JAK/STAT and NF-κB pathways, triggering a cytokine storm characterized by elevated IFN-γ, TNF-α, IL-6, and IL-10. This immune dysregulation, combined with impaired cytotoxic function, drives both lymphomagenesis and HLH progression. Current treatments remain unsatisfactory. Traditional HLH-directed regimens fail to control underlying lymphoma, while conventional lymphoma chemotherapy shows limited efficacy and poor tolerance due to multi-drug resistance and organ dysfunction.

Recently, targeted agents have emerged as promising strategies. Golidocitinib, a highly selective JAK1 inhibitor, effectively blocks JAK1-STAT3 signaling, suppresses EBV-driven tumor growth, and mitigates cytokine storms. It has demonstrated encouraging anti-tumor activity in relapsed/refractory NKTCL. Meanwhile, liposomal mitoxantrone improves tumor targeting and reduces cardiotoxicity, with objective response rates of 50%-60% in NKTCL. Etoposide, methylprednisolone, and pegaspargase further provide synergistic anti-lymphoma and anti-inflammatory effects.

Our research group has accumulated extensive experience in NKTCL and NKTCL-HLH, validating effective combination regimens and supporting the rationale of combining anti-lymphoma and anti-HLH strategies. Therefore, this study designed the innovative MEPL-G regimen (liposomal mitoxantrone, etoposide, methylprednisolone, pegaspargase, golidocitinib) for NKTCL-HLH patients. This regimen aims to rapidly control HLH, eradicate lymphoma, improve safety and tolerance, and ultimately prolong survival, addressing the urgent unmet medical need for this high-risk population.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China, 100730
        • Recruiting
        • Beijing Tongren Hospital, Capital Medical University
        • Principal Investigator:
          • Liang Wang, M.D.
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MEPL-G group

All enrolled patients may initiate induction therapy with the MEPL-G regimen after completing baseline imaging and laboratory examinations.

The detailed administration is as follows:

Doses of etoposide, golidocitinib, pegaspargase, and methylprednisolone are fixed. The optimal dose of liposomal mitoxantrone will be determined based on dose-limiting toxicity (DLT). In the Phase Ib part, 3 patients will be enrolled at the starting dose of liposomal mitoxantrone: 18 mg/m²/d on day 1, every 3 weeks (q3w). If no DLT occurs, the recommended phase 2 dose (RP2D) will be 18 mg/m²/d on day 1 q3w. If DLT occurs, the dose will be de-escalated sequentially. One cycle is 3 weeks, for a total of 6 cycles.

Patients achieving CR or PR after 2 cycles may be referred for allogeneic hematopoietic stem cell transplantation.

Patients with CR or PR after 2 cycles who are ineligible for transplantation may continue MEPL-G for a total of 6 cycles, followed by maintenance therapy with golidocitinib monotherapy
Drug: Mitoxantrone liposome
In the Phase Ib part, 3 patients will be enrolled at the starting dose of liposomal mitoxantrone: 18 mg/m²/d on day 1, every 3 weeks (q3w). If no DLT occurs, the recommended phase 2 dose (RP2D) will be 18 mg/m²/d on day 1 q3w. If DLT occurs, the dose will be de-escalated sequentially (18→16→14→12 mg/m²/d on day 1 q3w).
Drug: Etoposide
100mg/m²/d，d1、d8，q3w
Drug: Pegaspargase (PEG) Asparaginase
2000IU/m²/d，d5，q3w
Drug: methylprednisolone

15mg/kg/d，d1-3 7.5mg/kg/d，d4-7

1mg/kg/d d8-14 10mg/d，d15-21

Drug: golidocitinib
150mg/d，d1-d21，q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-month overall survival (OS) rate
Time Frame: From the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G
OS was defined from the date of initiation of MEPL-G to the date fo death.
From the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-month progression free survival (PFS) rate
Time Frame: From the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G
PFS was defined from the date of initiation of MEPL-G to the date of confirmed disease progression or death of any reason
From the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G
overall response rate (ORR)
Time Frame: from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G.
Overall response rate means sum of complete response rate and partial response rate
from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G.
complete response (CR) rate
Time Frame: from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G.
CR was defined as complete response evaluated using PET-CT scan
from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G
measured using CTCAE version 5.0
from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tongren Hospital

Investigators

  • Principal Investigator: Liang Wang, Beijing Tongren Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2026

Primary Completion (Estimated)

March 31, 2028

Study Completion (Estimated)

September 30, 2028

Study Registration Dates

First Submitted

April 7, 2026

First Submitted That Met QC Criteria

April 7, 2026

First Posted (Actual)

April 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRhos-NKTCL-HLH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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