Clinical trial NCT03533790: DEP-Ru Regimen as a Salvage Therapy for HLH
Official title: DEP-ruxolitinib Regimen as a Salvage Therapy for Refractory/Relapsed Hemophagocytic Lymphohistiocytosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hemophagocytic Lymphohistiocytosis
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
First posted: 2018-05-23
Enrollment: 80
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of treatment response
timeFrame: Change from before and 2,4,6 and 8 weeks after initiating DEP-Ru salvage therapy
Secondary outcomes:
measure: Survival
timeFrame: from the time patients received DEP-Ru salvage therapy up to 24 months or June 2021
measure: Adverse events that are related to treatment
timeFrame: through study completion, an average of 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
Study officials:
References:
citation: 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.
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-2015-05-644914. Epub 2015 Aug 19.
citation: Wang J, Zhang R, Wu X, Li F, Yang H, Liu L, Guo H, Zhang X, Mai H, Li H, Wang Z. Ruxolitinib-combined doxorubicin-etoposide-methylprednisolone regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis: a single-arm, multicentre, phase 2 trial. Br J Haematol. 2021 May;193(4):761-768. doi: 10.1111/bjh.17331. Epub 2021 Feb 9.