DEP-Ru Regimen as a Salvage Therapy for HLH

Hemophagocytic Lymphohistiocytosis Clinical Trial

Official title:

DEP-ruxolitinib Regimen as a Salvage Therapy for Refractory/Relapsed Hemophagocytic Lymphohistiocytosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03533790
• Other study ID #: DEP-Ru HLH
• Status: Recruiting
• Phase: Phase 3
• Start date: June 2018
• Est. completion date: June 2021

Study information

• Verified date: May 2018
• Source: Beijing Friendship Hospital
• Contact: jingshi wang
• Phone: 86-010-63139862
• Email: wangjingshi987[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aimed to investigate the efficacy and safety of ruxolitinib together with liposomal doxorubicin, etoposide and methylprednisolone (DEP-Ru) as a salvage therapy for refractory/relapsed hemophagocytic lymphohistiocytosis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 2021
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 70 Years

Eligibility

Inclusion Criteria:

1. meet HLH-04 diagnostic criteria;

2. treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least PR; or relapsed patients after remission;

3. Life expectancy exceeds 1 month;

4. Age=1 year old and =70 years old, gender is not limited;

5. Before the start of the study, total bilirubin = 10 times the upper limit of normal; serum creatinine = 1.5 times normal;

6. Serum HIV antigen or antibody negative;

7. HCV antibody is negative, or HCV antibody is positive, but HCV RNA is negative;

8. Both HBV surface antigen and HBV core antibody were negative. If any of the above is positive, peripheral blood hepatitis B virus DNA titer should be detected, and less than 1×103 copies/ml can enter the group;

9. Echocardiographic examination of LVEF = 50%;

10. 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. Serious mental illness;

8. Non-melanoma skin cancer history;

9. Patients unable to comply during the trial and/or follow-up phase;

10. Participate in other clinical research at the same time.

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Intervention

Drug:
• DEP-Ru
Drug: ruxolitinib Drug: doxorubicin Drug: etoposide Drug: methylprednisolone

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 (2)

Broglie L, Pommert L, Rao S, Thakar M, Phelan R, Margolis D, Talano J. Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis. Blood Adv. 2017 Aug 17;1(19):1533-1536. doi: 10.1182/bloodadvances.2017007526. eCollection 2017 Aug 22. — View Citation

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-2015-05-644 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of treatment response	A complete response was defined as normalization of all of the quantifiable symptoms and laboratory markers of HLH, including levels of sCD25, ferritin, and triglyceride; hemoglobin; neutrophil counts; platelet counts; and alanine aminotransferase (ALT). A partial response was defined as at least a 25% improvement in 2 or more quantifiable symptoms and laboratory markers as follows: sCD25 response was>1.5-fold decreased; ferritin and triglyceride 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 decrease of at least 50%.	Change from before and 2,4,6 and 8 weeks after initiating DEP-Ru salvage therapy
Secondary	Survival	survival	from the time patients received DEP-Ru salvage therapy up to 24 months or June 2021
Secondary	Adverse events that are related to treatment	Adverse events including myelosuppression, infection, bleeding and so on.	through study completion, an average of 2 years