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Pilot Study of Etoposide-based Therapy and Hematopoietic Cell Transplantation for Hemophagocytic Lymphohistiocytosis (HELA2012)

This study has been terminated.
(The PI resigned the institute, and the rest investigators at the institute decided to terminate the study.)
Information provided by (Responsible Party):
Dae-Young Kim, Asan Medical Center Identifier:
First received: February 29, 2012
Last updated: May 22, 2016
Last verified: May 2016
The investigators would like to propose a pilot study evaluating the efficacy of etoposide combined with immunosuppressive agents for adult secondary hemophagocytic lymphohistiocytosis (HLH), in order to prove out whether the modification of previous HLH-94 or HLH-2004 protocol for childhood patients can improve the outcome and decrease the toxicities. The results of this pilot study will be a base of a more-improved phase-2 protocol.

Condition Intervention
Hemophagocytic Lymphohistiocytosis
Drug: IST and/or alloHCT

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of First-line Immunosuppressive Therapy Combined With Etoposide and Allogeneic Hematopoietic Cell Transplantation in Refractory/Reactivated Cases for Hemophagocytic Lymphohistiocytosis (HLH) in Adult Patients

Resource links provided by NLM:

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • overall survival rate [ Time Frame: 1-year ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: 28 days ]
  • Complete response rate [ Time Frame: 56 days ]
  • Complete response rate [ Time Frame: 3 months ]
  • Partial response rate [ Time Frame: 28 days ]
  • Partial response rate [ Time Frame: 56 days ]
  • Partial response rate [ Time Frame: 3 months ]
  • reactivation-free survival rate [ Time Frame: 3 months ]
  • reactivation-free survival rate [ Time Frame: 6 months ]
  • overall survival rate [ Time Frame: 3 months ]
  • overall survival rate [ Time Frame: 6 months ]
  • overall survival rate [ Time Frame: 1 year ]
  • treatment-related mortality rate [ Time Frame: 1 year ]

Enrollment: 12
Study Start Date: March 2012
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IST and/or alloHCT
Patients who are newly diagnosed as HLH by HLH-2004 criteria, excluding those with HLH owing to malignancy or rheumatic disorder.
Drug: IST and/or alloHCT

1) Patients will be categorized by their initial serum ferritin level.

  1. Mild ( ferritin<3,000 μg/L): close observation
  2. Moderate (ferritin: 3,000-10,000 μg/L):

    1. Initiation : cyclosporine 3mg/kg + dexamethasone 10mg/m2/d po. or i.v. (D1-3)
    2. continuation: cyclosporine 3mg/kg p.o. bid (D4-56) + dexamethasone 10mg/m2/d (D4-14), then tapering.
  3. Severe (ferritin>10,000 μg/L):

    1. initiation : etoposide 100mg/m2/d i.v. + cyclosporine 2mg/kg i.v. q 12hours + dexamethasone 20mg/m2/d i.v. (D1-3)
    2. continuation : etoposide 100mg/m2/day weekly (D15-49) + cyclosporine 2mg/kg i.v. q 12 hours? ? po. (D4-56) + dexamethasone 10mg/m2/d (D4-14), 5mg/m2/d (D15-28), 2.5mg/m2/d (D29-42), 1.25mg/m2/d (D43-56), then tapering off.

      2) AlloHCT for refractory or reactivated cases.

Other Names:
  • Etoposide
  • Cyclosporine: Cipol
  • Dexamethasone
  • IV gammaglobulin

Detailed Description:
The treatment of HLH in adult patients has not been determined yet. Actually, we adopted the treatment protocol HLH2004, which was developed for pediatric HLH patients. The HLH2004 protocol, which is a potent and successful treatment for HLH, has shown some limitations in the treatment of adult HLH. First, the dose of etoposide is somewhat high for adult patients to tolerate. Second, the high incidence of opportunistic infection such as fungal, bacterial, and viral has threatened the patients. Third, more aggressive and intensive approach to adopt allogeneic hematopoietic cell transplantation will be needed earlier in adult patients. Based on these rationales, we developed a modified protocol based on HLH2004 to pit the treatment of adult HLH patients.

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients whose clinical findings satisfy 5 or more criteria out of the following 8 ones

    1. Fever ≥ 38.5 ℃ for ≥ 7 days
    2. Splenomegaly ≥ 3 FB below left subcostal margin
    3. Cytopenias affecting ≥ 2 of 3 lineages in PB Hb < 9 g/L Platelet < 100 x 109 /L ANC < 1.0 x 109 /L
    4. Hypertriglyceridemia and/or hypofibrinogenemia (fasting triglycerides ≥ 265 mg/dL, fibrinogen ≤ 1.5 g/L)
    5. Hemophagocytosis in BM or spleen or LN
    6. Low or absent NK-cell activity ( according to local laboratory reference)
    7. Serum-ferritin ≥ 500 mcg/L
    8. Soluble CD25(sIL-2 receptor) ≥ 2,400 U/ml
  • 18 years of age and over.
  • All patients (or his/her family when the patient cannot sign the consent form because of his/her general conditions) give written informed consent according to guidelines at institution's committee on human research.

Exclusion Criteria:

  • HLH from malignancy (such as lymphoma, myeloma, leukemia, and other solid tumor)
  • HLH from rheumatic disorder (such as SLE, AOSD, antiphospholipid antibody syndrome)
  • Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible
  • Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception
  • Male patient who reject the methods of avoiding pregnancy via methods such as abstinence, barrier method (condom etc).
  • Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)
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Please refer to this study by its identifier: NCT01547143

Korea, Republic of
Asan Medical center, University of Ulsan College of Medicine
Seoul, Korea, Republic of
Sponsors and Collaborators
Asan Medical Center
Principal Investigator: Dae-Young Kim, MD Asan Medical Center
  More Information


Responsible Party: Dae-Young Kim, Assistant Professor, Asan Medical Center Identifier: NCT01547143     History of Changes
Other Study ID Numbers: AMC-H-72
Study First Received: February 29, 2012
Last Updated: May 22, 2016

Keywords provided by Asan Medical Center:
Secondary hemophagocytic lymphohistiocytosis of adults

Additional relevant MeSH terms:
Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases
Dexamethasone acetate
Dexamethasone 21-phosphate
Etoposide phosphate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Immunosuppressive Agents processed this record on April 24, 2017