A Prospective Clinical Study of Ruxolitinib and Etoposide Combined With DDGP Regimen (RUE-DDGP) in Induction Therapy of T/NK Cell Lymphoma-associated Hemophagocytic Syndrome.

A Prospective Clinical Study of Ruxolitinib Phosphate Tablets and Etoposide Combined With DDGP Regimen (RUE-DDGP) in Induction Therapy of T/NK Cell Lymphoma-associated Hemophagocytic Syndrome.

To observe the efficacy and safety of Ruxolitinib and Etoposide combined with DDGP regimen ( cis-Platinum, Dexamethasone, Gemcitabine and Pegaspargase) in the first-line induction therapy of T cell lymphoma and NK/T cell lymphoma-associated hemophagocytic syndrome.

This is an open, one-arm, prospective clinical collaborative study. This study is aimed to observe the efficacy and safety of the new combined therapy of Ruxolitinib and Etoposide combined with DDGP regimen ( cis-Platinum, Dexamethasone, Gemcitabine and Pegaspargase) in the first-line induction therapy patients with primary central nervous system lymphoma. A total of 30 patients plan to participate in the study. The primary endpoint is objective remission rate (ORR) of hemophagocytic syndrome, and the secondary endpoints include progression-free survival (PFS) , objective remission rate (ORR) of lymphoma, overall survival (OS), and adverse events(ADR).

Inclusion Criteria:

1. Histopathologically proven T-cell lymphoma or NK/ T-cell lymphoma;

2. Comply with HLH-2004 diagnostic criteria;Hemophagocytic syndrome can be diagnosed when either of the following two criteria is met:

   A. Molecular diagnosis is consistent with hemophagocytic syndrome. Pathological mutations were found in known pathogenic genes related to hemophagocytic syndrome, such as PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A, BIRC4, ITK, AP3B1, MAGT1, CD27, etc.

   B. Meet 5 of the following 8 indicators I. Fever: The body temperature was > 38.5℃, lasting > for 7 days. II. Splenomegaly . III. Hemocytopenia (involving two or three lines of peripheral blood) : hemoglobin < 90g/L, platelet < 100×10^9/L, neutrophils < 1.0×10^9/L and not caused by reduced hematopoietic function of bone marrow.

   IV. Hypertriglyceridemia and/or hypofibrinogenemia: triglyceride > 3mmol/L or 3 standard deviations higher than the same age, fibrinogen < 1.5g/L or 3 standard deviations lower than the same age.

   V. Hemophagocytes are found in bone marrow, spleen, liver, or lymph nodes. VI.NK cell activity decreased or absent. VII. Elevated serum ferritin: ferritin ≥500μg/L. VIII. Elevated sCD25 (soluble interleukin-2 receptor).

3. Ages 14-75 years.

4. Expected survival of more than 1 week.

5. Patients with left ventricular ejection fraction > 50%, no major bleeding of active internal organs (digestive tract, lung, brain, etc.), and oxygenation index > 250.

6. Patients have good compliance with the planned treatment and follow-up, can understand the research process of this study and sign the written informed consent.

Exclusion Criteria:

1. Three or more drugs including ruxolitinb, etoposide, pemasparase, gemcitabine or cisplatin were used simultaneously in the previous 28 days.
2. Pregnant or lactating women and patients of reproductive age who refuse to take appropriate contraceptive measures during the course of this study. If the patient was male, they refused to use adequate contraception or sperm donation during the study period and for 3 months after the last study of lymphoma-related chemotherapy drugs.
3. Allergic to any medication in the program.
4. Grade III or IV heart disease based on the New York Heart Association (NYHA) score.
5. Major active bleeding of internal organs (including gastrointestinal bleeding, alveolar bleeding, intracranial bleeding, etc.).
6. Acute pancreatitis.
7. People infected with HIV (HIV antibody positive).
8. HBV DNA copy number is >10^4/ml in patients with acute or chronic active hepatitis B, and HBV DNA copy number is >10^4/ml in patients with acute or chronic active hepatitis C (HCV antibody positive, HCV RNA negative acceptable).
9. Participate in other clinical investigators.
10. The investigators identified patients who were not eligible for the study.