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DEP-Ru Regimen as a Salvage Therapy for HLH

Primary Purpose

Hemophagocytic Lymphohistiocytosis

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
DEP-Ru
Sponsored by
Beijing Friendship Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophagocytic Lymphohistiocytosis

Eligibility Criteria

1 Year - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beijing Friendship Hospital, Capital Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DEP-Ru

Arm Description

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.

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

Survival
survival
Adverse events that are related to treatment
Adverse events including myelosuppression, infection, bleeding and so on.

Full Information

First Posted
May 12, 2018
Last Updated
May 26, 2018
Sponsor
Beijing Friendship Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03533790
Brief Title
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

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
June 2018 (Anticipated)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beijing Friendship Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophagocytic Lymphohistiocytosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DEP-Ru
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DEP-Ru
Intervention Description
Drug: ruxolitinib Drug: doxorubicin Drug: etoposide Drug: methylprednisolone
Primary Outcome Measure Information:
Title
Evaluation of treatment response
Description
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%.
Time Frame
Change from before and 2,4,6 and 8 weeks after initiating DEP-Ru salvage therapy
Secondary Outcome Measure Information:
Title
Survival
Description
survival
Time Frame
from the time patients received DEP-Ru salvage therapy up to 24 months or June 2021
Title
Adverse events that are related to treatment
Description
Adverse events including myelosuppression, infection, bleeding and so on.
Time Frame
through study completion, an average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
jingshi wang
Phone
86-010-63139862
Email
wangjingshi987@126.com
Facility Information:
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100050
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jingshi wang, M.M.
Phone
86-13520280731
Email
wangjingshi987@126.com

12. IPD Sharing Statement

Citations:
PubMed Identifier
29296794
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.
Results Reference
background
PubMed Identifier
26289641
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.
Results Reference
result
PubMed Identifier
33559893
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.
Results Reference
derived

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DEP-Ru Regimen as a Salvage Therapy for HLH

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