Epstein-Barr Virus, Hemophagocytic Lymphohistiocytosis, Lymphoma, PD-1 Antibody
Conditions
Brief summary
The efficacy and safety of L-DEP (aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.
Detailed description
Lymphoma-associated hemophagocytic lympohistiocytosis is a refractory immune disorder with high mortality. Without early intervention, the median survival time is less than 2 months. Currently, HLH-94 or HLH-04 are the standard HLH treatment regimens, which have improved the disease response rate to approximately 70% and increased the 5-year OS rate to 50%. However, approximately, 30% of the patients remain unresponsive to standard therapy, especially if HLH is lymphoma-associated. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of L-DEP (aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.
Interventions
Doxorubicin (doxorubicin hydrochloride liposome injection) 35 mg/m2 day 1; etoposide 75 mg/m2 day1; methylprednisolone 1.5mg/kg days 1 to 3, 0.25mg/kg day 4 to 14;aspargase 6000iu/m2 day2, day4; PD-1 antibody injection 200mg day 5.
Sponsors
Beijing Friendship Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed as lymphoma-Hemophagocytic Lymphohistiocytosis. * EBV-DNA in peripheral blood \> 1000 copies/ml or EBER detected in tissue specimens. * Age 18\~70，gender is not limited. * Estimated survival time ≥ 1 month. * Cardiac ultrasound LVEF≥50%; No Active bleeding of the internal organs(digestive tract, lung, brain, etc.); If the patient has dyspnea, oxygenation index \>250. * Signed informed consent.
Exclusion criteria
* Heart function above grade II (NYHA). * Severe myocardial injury：TNT、TNI、CK-MB \> 3 ULN. * Accumulated dose of doxorubicin above 400mg/m2 、epirubicin above 750mg/m2、pirarubicin above 800mg/m2 or the patients treated with anthracycline induced cardiovascular disease. * Pregnancy or lactating Women. * Allergic to pegylated liposomal doxorubicin，etoposide，or PD-1 antibody. * Thyroid dysfunction. * HIV antibody positivity. * Acute or chronic active hepatitis B (HBsAg positivity, HBV DNA negative acceptable), acute or chronic active hepatitis C (HCV antibody negatively acceptable; HCV antibody positivity, HCV RNA negative acceptable). * Participate in other clinical research at the same time. * The researchers considered that patients are not suitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response rate | Two weeks after initiation of L-DEP regimen combined with PD-1 antibody | complete response (CR) and partial response (PR) rates |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EBV-DNA clearance at 2 and 4weeks | 4 weeks after induction | EBV-DNA clearance at 2 and 4weeks |
| Overall Survival | 1 years | from the date of inclusion to date of death, irrespective of cause |
| Adverse Events | 30 days after last administration of cytotoxic drugs | any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORZhao Wang, MD
Beijing Friendship Hospital
Outcome results
None listed