Trial of DA-EPOCH Regimen for NHL With HLH

Sponsor

The First Affiliated Hospital with Nanjing Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01818908

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
NHL With Hemophagocytic Lymphohistiocytosis	Drug: DA-EPOCH	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Oct 1, 2018

Anticipated Study Completion Date :

Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: DA-EPOCH DA-EPOCH regimen Other Names: Infused agents Etoposide Doxorubicin Vincristine Cyclophosphamide Prednisone Rituximab(B-NHL)

Arm

Intervention/Treatment

Experimental: 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.

Drug: DA-EPOCH

DA-EPOCH regimen

Other Names:

Infused agents

Etoposide

Doxorubicin

Vincristine

Cyclophosphamide

Prednisone

Rituximab(B-NHL)

Outcome Measures

Primary Outcome Measures

overall response rate [one year]
overall response rate after treated by DA-EPOCH regimen

Secondary Outcome Measures

progression free survival [one year]
progression free survival after treatment of DA-EPOCH regimen
overall survival [one year]
overall 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

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ChangZhou No.2 People's Hospital	ChangZhou	Jiangsu	China	213011
2	HuaiAn First People's Hospital	HuaiAn	Jiangsu	China	223300
3	JiangSu Province Hospital	NanJing	Jiangsu	China	210029
4	WuXi People's Hospital	WuXi	Jiangsu	China	214023