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Trial of DA-EPOCH Regimen for NHL With HLH

Primary Purpose

NHL With Hemophagocytic Lymphohistiocytosis

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
DA-EPOCH
Sponsored by
The First Affiliated Hospital with Nanjing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for NHL With Hemophagocytic Lymphohistiocytosis focused on measuring non-Hodgkin's lymphoma, hemophagocytic lymphohistiocytosis, DA-EPOCH, rituximab

Eligibility Criteria

15 Years - 80 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

1 .Histologically confirmed non-Hodgkin's lymphoma; 2. Patients whose clinical findings satisfy either of HLH 2004 standard: 3. newly-diagnosed and untreated; 4. understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements.

HLH2004 standard at least 5 criteria out of the following: Fever ≥ 38.5 ℃ for ≥ 7 days; hepatosplenomegaly; Cytopenias affecting ≥ 2 of 3 lineages in PB Hb < 9 g/L Platelet < 100 x 109 /L ANC < 1.0 x 109 /L; Hypertriglyceridemia and/or hypofibrinogenemia (fasting triglycerides ≥ 265 mg/dL, fibrinogen ≤ 1.5 g/L); Hemophagocytosis in BM or spleen or LN; Low or absent NK-cell activity ( according to local laboratory reference); Serum-ferritin ≥ 500 mcg/L ; Soluble CD25(sIL-2 receptor) ≥ 2,400 U/ml ; 3.New-diagnosed and untreated; 4.Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria

  1. primary HLH;
  2. HLH from rheumatic disorder (such as systemic Lupus Erythematosus, adult onset still disease, antiphospholipid antibody syndrome);
  3. pregnancy (as determined by serum or urine test) or active breast feeding;
  4. concomitant malignancy other than NHL and need to treat;
  5. concomitant with other hematologic diseases (such as leukemia, hemophilia primary myelofibrosis) which investigators considered it unsuitable to be enrolled into this clinical trial;
  6. any potential drug abuse, medical, psychological or social conditions which may disturb this investigation and assessment;
  7. in any conditions which investigator considered ineligible for this study

Sites / Locations

  • ChangZhou No.2 People's Hospital
  • HuaiAn First People's Hospital
  • JiangSu Province Hospital
  • WuXi People's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DA-EPOCH

Arm Description

Infused agents: Etoposide 50 mg/m2/day CI24h d1-d4; Doxorubicin 10 mg/m2/day CI24h d1-d4; Vincristine 0.4mg/m2/day CI24h d1-d4; Bolus agents: Rituximab(B-NHL) 375 mg/m2/day IV d0; Cyclophosphamide 750 mg/m2/day IV d5 ; Prednisone 60 mg/m2/bid oral or IV d1-d5; The details of dose adjustment are described in ref 1. If enrolled patient was histologically confirmed CD20+ B cell lymphoma, standard dose of rituximab will be recommend to combined with DA-EPOCH regimen.

Outcomes

Primary Outcome Measures

overall response rate
overall response rate after treated by DA-EPOCH regimen

Secondary Outcome Measures

progression free survival
progression free survival after treatment of DA-EPOCH regimen
overall survival
overall survival after treatment of DA-EPOCH regimen
Number of Participants with Adverse Events
Number of Participants with Adverse Events, and evaluated standard is according to common terminology criteria adverse events(CTCAE) version 4.0

Full Information

First Posted
March 23, 2013
Last Updated
February 13, 2019
Sponsor
The First Affiliated Hospital with Nanjing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT01818908
Brief Title
Trial of DA-EPOCH Regimen for NHL With HLH
Official Title
A Prospective, Single-arm, Open-label, Phase 2 Study to Evaluate Efficacy and Safety of DA-EPOCH Regimen for Non-Hodgkin's Lymphoma With Hemophagocytic Lymphohistiocytosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 2012 (undefined)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
April 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The major purpose of this clinical study is to assess clinical outcome of dose-adjusted EPOCH regimen for patients with non-Hodgkin's lymphoma(NHL)-associated hemophagocytic lymphohistiocytosis
Detailed Description
Lymphoma-associated hemophagocytic lymphohistiocytosis(LA-HLH) has a high fatality rate and the worst outcome. The major cause of LA-HLH is aggressive non-Hodgkin's lymphoma(NHL), especially T/NKT cell lymphomas. Until now, there is no recommended therapeutic schedule for this fatal disease. Dose-adjusted(DA) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) shows effective activity in patients with aggressive NHL, which also contains the critical drugs for HLH of HLH-94/04. The investigators therefore developed DA-EPOCH regimen to treat non-Hodgkin's lymphoma with hemophagocytic lymphohistiocytosis and assess its clinical outcome including safety and efficacy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
NHL With Hemophagocytic Lymphohistiocytosis
Keywords
non-Hodgkin's lymphoma, hemophagocytic lymphohistiocytosis, DA-EPOCH, rituximab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DA-EPOCH
Arm Type
Experimental
Arm Description
Infused agents: Etoposide 50 mg/m2/day CI24h d1-d4; Doxorubicin 10 mg/m2/day CI24h d1-d4; Vincristine 0.4mg/m2/day CI24h d1-d4; Bolus agents: Rituximab(B-NHL) 375 mg/m2/day IV d0; Cyclophosphamide 750 mg/m2/day IV d5 ; Prednisone 60 mg/m2/bid oral or IV d1-d5; The details of dose adjustment are described in ref 1. If enrolled patient was histologically confirmed CD20+ B cell lymphoma, standard dose of rituximab will be recommend to combined with DA-EPOCH regimen.
Intervention Type
Drug
Intervention Name(s)
DA-EPOCH
Other Intervention Name(s)
Infused agents, Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, Prednisone, Rituximab(B-NHL)
Intervention Description
DA-EPOCH regimen
Primary Outcome Measure Information:
Title
overall response rate
Description
overall response rate after treated by DA-EPOCH regimen
Time Frame
one year
Secondary Outcome Measure Information:
Title
progression free survival
Description
progression free survival after treatment of DA-EPOCH regimen
Time Frame
one year
Title
overall survival
Description
overall survival after treatment of DA-EPOCH regimen
Time Frame
one year
Title
Number of Participants with Adverse Events
Description
Number of Participants with Adverse Events, and evaluated standard is according to common terminology criteria adverse events(CTCAE) version 4.0
Time Frame
up to 30 days after last dose of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 1 .Histologically confirmed non-Hodgkin's lymphoma; 2. Patients whose clinical findings satisfy either of HLH 2004 standard: 3. newly-diagnosed and untreated; 4. understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements. HLH2004 standard at least 5 criteria out of the following: Fever ≥ 38.5 ℃ for ≥ 7 days; hepatosplenomegaly; Cytopenias affecting ≥ 2 of 3 lineages in PB Hb < 9 g/L Platelet < 100 x 109 /L ANC < 1.0 x 109 /L; Hypertriglyceridemia and/or hypofibrinogenemia (fasting triglycerides ≥ 265 mg/dL, fibrinogen ≤ 1.5 g/L); Hemophagocytosis in BM or spleen or LN; Low or absent NK-cell activity ( according to local laboratory reference); Serum-ferritin ≥ 500 mcg/L ; Soluble CD25(sIL-2 receptor) ≥ 2,400 U/ml ; 3.New-diagnosed and untreated; 4.Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements. Exclusion criteria primary HLH; HLH from rheumatic disorder (such as systemic Lupus Erythematosus, adult onset still disease, antiphospholipid antibody syndrome); pregnancy (as determined by serum or urine test) or active breast feeding; concomitant malignancy other than NHL and need to treat; concomitant with other hematologic diseases (such as leukemia, hemophilia primary myelofibrosis) which investigators considered it unsuitable to be enrolled into this clinical trial; any potential drug abuse, medical, psychological or social conditions which may disturb this investigation and assessment; in any conditions which investigator considered ineligible for this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Xu, M.D., Ph.D.
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
ChangZhou No.2 People's Hospital
City
ChangZhou
State/Province
Jiangsu
ZIP/Postal Code
213011
Country
China
Facility Name
HuaiAn First People's Hospital
City
HuaiAn
State/Province
Jiangsu
ZIP/Postal Code
223300
Country
China
Facility Name
JiangSu Province Hospital
City
NanJing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
WuXi People's Hospital
City
WuXi
State/Province
Jiangsu
ZIP/Postal Code
214023
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
11929754
Citation
Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. doi: 10.1182/blood.v99.8.2685.
Results Reference
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PubMed Identifier
16937360
Citation
Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039.
Results Reference
background
PubMed Identifier
18378569
Citation
Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. doi: 10.1200/JCO.2007.13.1391. Epub 2008 Mar 31.
Results Reference
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Trial of DA-EPOCH Regimen for NHL With HLH

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