DEP-Ru Regimen as a Salvage Therapy for HLH

NCT03533790 | Unknown Phase 3 DMC

• 1 other identifier: DEP-Ru HLH
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophagocytic Lymphohistiocytosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Survival

  from the time patients received DEP-Ru salvage therapy up to 24 months or June 2021

• Adverse events that are related to treatment

  through study completion, an average of 2 years

Study Arms (1)

DEP-Ru

EXPERIMENTAL

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.

Drug: DEP-Ru

Interventions

DEP-Ru DRUG

* Drug: ruxolitinib * Drug: doxorubicin * Drug: etoposide * Drug: methylprednisolone

DEP-Ru

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• meet HLH-04 diagnostic criteria;
• treated with HLH-94 no less than 2 weeks before enrollment and did not achieve at least PR; or relapsed patients after remission；
• Life expectancy exceeds 1 month;
• Age≥1 year old and ≤70 years old, gender is not limited；
• Before the start of the study, total bilirubin ≤ 10 times the upper limit of normal; serum creatinine ≤ 1.5 times normal；
• Serum HIV antigen or antibody negative；
• HCV antibody is negative, or HCV antibody is positive, but HCV RNA is negative；
• 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；
• Echocardiographic examination of LVEF ≥ 50%;
• Informed consent.

You may not qualify if:

• Heart function above grade II (NYHA)；
• Accumulated dose of doxorubicin above 300mg/m2 or epirubicin above 450mg/m2；
• Pregnancy or lactating Women；
• Allergic to Pegaspargase, doxorubicin or etoposide；
• Active bleeding of the internal organs；
• uncontrollable infection；
• Serious mental illness;
• Non-melanoma skin cancer history;
• Patients unable to comply during the trial and/or follow-up phase;
• Participate in other clinical research at the same time.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

RECRUITING

Related Publications (3)

• 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.

  PMID: 29296794 BACKGROUND

• 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.

  PMID: 26289641 RESULT

• 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.

  PMID: 33559893 DERIVED

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

jingshi wang

CONTACT

86-010-63139862; wangjingshi987@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: May 12, 2018
• First Posted: May 23, 2018
• Study Start: June 1, 2018
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2021
• Last Updated: May 30, 2018

Record last verified: 2018-05

Locations

CN (1)