DEP-Ru Regimen as a Salvage Therapy for HLH

Phase 3

• Conditions: Hemophagocytic Lymphohistiocytosis
• Interventions: Drug: DEP-Ru

• Registration Number: NCT03533790
• Lead Sponsor: Beijing Friendship Hospital

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2018-05
• Study First Submitted: 2018-05-12
• Study First Submitted QC: 2018-05-12
• Study First Posted: 2018-05-23
• Last Update Submitted: 2018-05-26
• Last Update Posted: 2018-05-30
• Study Start: 2018-06
• Primary Completion: 2018-06
• Study Completion: 2021-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DEP-Ru	DEP-Ru	doxorubicin (doxorubicin hydrochloride liposome injection) 25 mg/m2 day 1; etoposide 100 mg/m2 was administered day1; methylprednisolone 2 mg/kg days 1 to 5,then gradually reduce; ruxolitinib 0.3mg/kg/d。This regimen was repeated after 2 weeks.

Primary Outcome Measures

Name	Time	Method
Evaluation of treatment response	Change from before and 2,4,6 and 8 weeks after initiating DEP-Ru salvage therapy	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%.

Secondary Outcome Measures

Name	Time	Method
Survival	from the time patients received DEP-Ru salvage therapy up to 24 months or June 2021	survival
Adverse events that are related to treatment	through study completion, an average of 2 years	Adverse events including myelosuppression, infection, bleeding and so on.

Trial Locations

Locations (1)

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China