Trial of DA-EPOCH Regimen for NHL With HLH

This study is currently recruiting participants.
Verified March 2013 by Jiangsu Province Hospital
Sponsor:
Information provided by (Responsible Party):
WEI XU, Jiangsu Province Hospital
ClinicalTrials.gov Identifier:
NCT01818908
First received: March 23, 2013
Last updated: NA
Last verified: March 2013
History: No changes posted
  Purpose

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 Intervention Phase
NHL With Hemophagocytic Lymphohistiocytosis
Drug: DA-EPOCH
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Study of Dose-adjusted EPOCH Regimen for Non-Hodgkin's Lymphoma With Hemophagocytic Lymphohistiocytosis

Resource links provided by NLM:


Further study details as provided by Jiangsu Province Hospital:

Primary Outcome Measures:
  • overall response rate [ Time Frame: one year ] [ Designated as safety issue: No ]
    overall response rate after treated by DA-EPOCH regimen

  • Time to Response [ Time Frame: four weekd after treatment of DA-EPOCH ] [ Designated as safety issue: No ]
    To determine the median time to overall response


Secondary Outcome Measures:
  • progression free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
    progression free survival after treatment of DA-EPOCH regimen

  • overall survival [ Time Frame: one year ] [ Designated as safety issue: No ]
    overall survival after treatment of DA-EPOCH regimen

  • Number of Participants with Adverse Events [ Time Frame: up to 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
    Number of Participants with Adverse Events, and evaluated standard is according to common terminology criteria adverse events(CTCAE) version 4.0


Estimated Enrollment: 50
Study Start Date: June 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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. 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

Ages Eligible for Study:   15 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Histologically confirmed non-Hodgkin's lymphoma;
  2. Patients whose clinical findings satisfy either of HLH 2004 standard or ASH2009 standard:

    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.

ASH2009 Standard

  1. .At least 3 of 4:

    1. Fever
    2. Splenomegaly
    3. Cytopenias (minimum 2 cell lines reduced)
    4. Hepatitis
  2. . And at least 1 of 4:

    1. Hemophagocytosis
    2. ↑ Ferritin
    3. ↑ sIL2Rα (age based)
    4. Absent or very decreased NK function 4. Other results supportive of HLH diagnosis:
    1. Hypertriglyceridemia
    2. Hypofibrinogenemia
    3. Hyponatremia

Exclusion Criteria:

  1. Primary HLH.
  2. HLH from rheumatic disorder (such as SLE, AOSD, antiphospholipid antibody syndrome)
  3. Pregnancy (as determined by serum or urine test) or active breast feeding
  4. Concomitant malignancy other than non-Hodgkin's lymphoma and need to treat;
  5. Concomitant with other hematologic diseases(such as leukemia,hemophilia primary myelofibrosis) which investigator 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01818908

Contacts
Contact: LEI FAN, M.D., Ph.D. +86 25 6813 6034 fanlei_fl@yahoo.com.cn

Locations
China, Jiangsu
ChangZhou No.2 People's Hospital Recruiting
ChangZhou, Jiangsu, China, 213011
Contact: Min Zhou, Dr.         
Principal Investigator: Min Zhou, M.D.         
HuaiAn First People's Hospital Recruiting
HuaiAn, Jiangsu, China, 223300
Contact: Liang Yu, Dr.         
Principal Investigator: Liang Yu, M.D., Ph.D.         
JiangSu Province Hospital Recruiting
NanJing, Jiangsu, China, 210029
Contact: LEI FAN, Dr.    86 25 6813 6034      
Principal Investigator: WEI XU, M.D., Ph.D.         
WuXi People's Hospital Recruiting
WuXi, Jiangsu, China, 214023
Contact: Yun Zhuang, M.D.         
Principal Investigator: YunFeng Shen, M.D., Ph.D.         
Sponsors and Collaborators
Jiangsu Province Hospital
Investigators
Principal Investigator: Wei Xu, M.D., Ph.D. Jiangsu Province Hospital
  More Information

Publications:
Responsible Party: WEI XU, Professor, Jiangsu Province Hospital
ClinicalTrials.gov Identifier: NCT01818908     History of Changes
Other Study ID Numbers: JSPH-HLH-001
Study First Received: March 23, 2013
Last Updated: March 23, 2013
Health Authority: China: Ministry of Health

Keywords provided by Jiangsu Province Hospital:
non-Hodgkin's lymphoma
hemophagocytic lymphohistiocytosis
DA-EPOCH
rituximab

Additional relevant MeSH terms:
Lymphohistiocytosis, Hemophagocytic
Lymphoma, Non-Hodgkin
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 16, 2014