L-DEP as an Initial Treatment for EBV-HLH

Hemophagocytic Lymphohistiocytosis Clinical Trial

Official title:

A Randomized Controlled Trial of L-DEP as an Initial Treatment for Epstein-Barr Virus-associated Hemophagocytic Lymphohistiocytosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02912702
• Other study ID #: L-DEP-EBV-HLH-First line
• Status: Recruiting
• Phase: Phase 3
• First received: September 9, 2016
• Last updated: September 21, 2016
• Start date: September 2016
• Est. completion date: September 2019

Study information

• Verified date: September 2016
• Source: Beijing Friendship Hospital
• Contact: jingshi wang, M.M.
• Phone: 86-13520280731
• Email: wangjingshi987[@]sina.com
• Is FDA regulated: No
• Health authority: China: Beijing Municipal Health Bureau
• Study type: Interventional

Clinical Trial Summary

This study aimed to investigate the efficacy and safety of Pegaspargase together with liposomal doxorubicin, etoposide and high dose methylprednisolone (L-DEP) as an initial treatment for Epstein Barr virus-induced hemophagocytic lymphohistiocytosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 2019
• Est. primary completion date: September 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients were older than 14 years of age

2. Diagnosed as EBV-Hemophagocytic Lymphohistiocytosis (HLH)

3. Patients did not receive any treatment for HLH before

4. Informed consent

Exclusion Criteria:

1. Heart function above grade II (NYHA)

2. Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2

3. Pregnancy or lactating Women

4. Allergic to Pegaspargase, doxorubicin or etoposide

5. Active bleeding of the internal organs

6. uncontrollable infection

7. history of acute and chronic pancreatitis

8. Participate in other clinical research at the same time

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Intervention

Drug:
• Pegaspargase
2000U/m2 day5
• doxorubicin hydrochloride liposome injection
25 mg/m2 day 1
• etoposide
100 mg/m2 was administered once on the first day of every week
• methylprednisolone
15 mg/kg days 1 to 3, 0.75 mg/kg days 4 to 7
• Etoposide
150 mg/m2 twice weekly for 2 weeks and then weekly
• dexamethasone
initially 10 mg/m2 for 2 weeks followed by 5 mg/m2 for 2 weeks, 2.5 mg/m2 for 2 weeks, 1.25 mg/m2 for one week, and one week of tapering

Locations

Country	Name	City	State
China	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Friendship Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

Wang Y, Huang W, Hu L, Cen X, Li L, Wang J, Shen J, Wei N, Wang Z. Multicenter study of combination DEP regimen as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis. Blood. 2015 Nov 5;126(19):2186-92. doi: 10.1182/blood-2015-05-644914. Epub 2015 Aug 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response(complete response+ partial response) rate of Participants	A complete response was defined as normalization of all of the quantifiable symptoms and laboratory markers of HLH, including levels of sCD25(pg/ml), ferritin(µg/L), and triglyceride(mmol/L); hemoglobin(g/L); neutrophil counts(×109/L); platelet counts(×109/L); and alanine aminotransferase (ALT(U/L)).; A partial response was defined as at least a 25% improvement in 2 or more quantifiable symptoms and laboratory markers as follows: sCD25(pg/ml) response was>1.5-fold decreased; ferritin (µg/L)and triglyceride(mmol/L) decreased at least 25%; for patients with an initial neutrophil count of<0.5 ×109/L, a response was defined as an increase by at least 100% to>0.5× 109/L; for patients with a neutrophil count of 0.5 to 2.0 × 109/L, an increase by at least 100% to >2.0 × 109/L was considered a response; and for patients with ALT >400 U/L, response was defined as an ALT (U/L)decrease of at least 50%.	Change from before and 2,4,6 and 8 weeks after initiating L-DEP or HLH-94 therapy	No
Secondary	Compare survival between two arms		from the time patients received L-DEP or HLH-94 therapy up to 12 months or September 2019	No
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse events including pancreatitis, liver function damage, myelosuppression, infection, bleeding and so on.	through study completion, an average of 1 years	Yes
Secondary	Change of Epstein-Barr virus(EBV)-DNA before and after therapy		Change from before and 2, 4, 6 and 8 weeks after initiating L-DEP or HLH-94 therapy	No