Trial of DA-EPOCH Regimen for NHL With HLH

Phase 2

• Conditions: NHL With Hemophagocytic Lymphohistiocytosis
• Interventions: Drug: DA-EPOCH

• Registration Number: NCT01818908
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

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.

Study Timeline

• Study Start: 2012-06
• Study First Submitted: 2013-03-23
• Study First Submitted QC: 2013-03-23
• Study First Posted: 2013-03-27
• Primary Completion: 2018-10
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-13
• Last Update Posted: 2019-02-15
• Study Completion: 2019-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DA-EPOCH	DA-EPOCH	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.

Primary Outcome Measures

Name	Time	Method
overall response rate	one year	overall response rate after treated by DA-EPOCH regimen

Secondary Outcome Measures

Name	Time	Method
overall survival	one year	overall survival after treatment of DA-EPOCH regimen
progression free survival	one year	progression free survival after treatment of DA-EPOCH regimen
Number of Participants with Adverse Events	up to 30 days after last dose of treatment	Number of Participants with Adverse Events, and evaluated standard is according to common terminology criteria adverse events(CTCAE) version 4.0

Trial Locations

Locations (4)

HuaiAn First People's Hospital; 🇨🇳 HuaiAn, Jiangsu, China

JiangSu Province Hospital; 🇨🇳 NanJing, Jiangsu, China

ChangZhou No.2 People's Hospital; 🇨🇳 ChangZhou, Jiangsu, China

WuXi People's Hospital; 🇨🇳 WuXi, Jiangsu, China