Clinical trial NCT01818908: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: NHL With Hemophagocytic Lymphohistiocytosis
Keywords: non-Hodgkin's lymphoma
hemophagocytic lymphohistiocytosis
DA-EPOCH
rituximab
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2013-03-27
Enrollment: 50
Sex: ALL
Minimum age (years): 15
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

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

Primary outcomes:
measure: overall response rate
timeFrame: one year
Secondary outcomes:
measure: progression free survival
timeFrame: one year
measure: overall survival
timeFrame: one year
measure: Number of Participants with Adverse Events
timeFrame: up to 30 days after last dose of treatment
Other outcomes:
Locations:
city: ChangZhou
country: China
facility: ChangZhou No.2 People's Hospital
state: Jiangsu
city: HuaiAn
country: China
facility: HuaiAn First People's Hospital
state: Jiangsu
city: NanJing
country: China
facility: JiangSu Province Hospital
state: Jiangsu
city: WuXi
country: China
facility: WuXi People's Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Wei Xu, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.