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)

NCT07525466 | Recruiting Phase 1

• 1 other identifier: TRhos-NKTCL-HLH
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Extranodal NK T Cell Lymphoma; Hemophagocytic Lymphohistiocytosis (HLH)

Keywords

extranodal NK/T-cell lymphoma; hemophagocytic lymphohistiocytosis; Mitoxantrone Liposome; Golidocitinib; JAK1

Outcome Measures

Primary Outcomes (1)

• 6-month overall survival (OS) rate

  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 Outcomes (4)

• 6-month progression free survival (PFS) rate

  From the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G

• overall response rate (ORR)

  from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G.

• complete response (CR) rate

  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]

  from the date of initiation of MEPL-G as of 6 months after initiation of MEPL-G

Study Arms (1)

MEPL-G group

EXPERIMENTAL

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; Drug: Etoposide; Drug: Pegaspargase (PEG) Asparaginase; Drug: methylprednisolone; Drug: golidocitinib

Interventions

Mitoxantrone liposome DRUG

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).

MEPL-G group

Etoposide DRUG

100mg/m²/d，d1、d8，q3w

MEPL-G group

Pegaspargase (PEG) Asparaginase DRUG

2000IU/m²/d，d5，q3w

MEPL-G group

methylprednisolone DRUG

15mg/kg/d，d1-3 7.5mg/kg/d，d4-7 1mg/kg/d d8-14 10mg/d，d15-21

MEPL-G group

golidocitinib DRUG

150mg/d，d1-d21，q3w

MEPL-G group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (1)

Beijing Tongren Hospital, Capital Medical University

Beijing, 100730, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Lymphohistiocytosis, Hemophagocytic

Interventions

Etoposide; pegaspargase; Asparaginase; Methylprednisolone

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Liang Wang

  Beijing Tongren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liang Wang, M.D.

CONTACT

+861058266633; wangliangtrhos@126.com

Jia Cong, M.D.

CONTACT

congjia21@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Hematology in Beijing Tongren Hospital

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)