L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH
Study Details
Study Description
Brief Summary
The efficacy and safety of L-DEP (PEG-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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 (PEG-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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: L-DEP and PD-1 antibody PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone administered in 2 week cycles for 2 cycles |
Drug: L-DEP and PD-1 antibody
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; PEG-aspargase 6000iu/m2 day2, day4; PD-1 antibody injection 200mg day 5.
|
Outcome Measures
Primary Outcome Measures
- Response rate [Two weeks after initiation of L-DEP regimen combined with PD-1 antibody]
complete response (CR) and partial response (PR) rates
Secondary Outcome Measures
- Response rate of lymphoma [Four weeks after second cycle of L-DEP and PD-1 antibody regimen]
complete response (CR) and partial response (PR) rates, using the standard response criteria
- Progression Free Survival [1 years]
from date of inclusion to date of progression, relapse, or death from any cause
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosed as lymphoma-Hemophagocytic Lymphohistiocytosis.
-
EBV-DNA in peripheral blood > 1000 copies/ml or EBER detected in tissue specimens.
-
Age 18~65，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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Friendship Hospital, Capital Medical University | Beijing | Beijing | China | 100050 |
Sponsors and Collaborators
- Beijing Friendship Hospital
Investigators
- Principal Investigator: Zhao Wang, MD, Beijing Friendship Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BFH20220920001