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

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ClinicalTrials.gov Identifier: NCT01547143
Recruitment Status : Terminated (The PI resigned the institute, and the rest investigators at the institute decided to terminate the study.)
First Posted : March 7, 2012
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Dae-Young Kim, Asan Medical Center

Tracking Information
First Submitted Date  ICMJE February 29, 2012
First Posted Date  ICMJE March 7, 2012
Last Update Posted Date July 20, 2018
Study Start Date  ICMJE March 2012
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2012)
overall survival rate [ Time Frame: 1-year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01547143 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2012)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Etoposide-based Therapy and Hematopoietic Cell Transplantation for Hemophagocytic Lymphohistiocytosis
Official Title  ICMJE 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophagocytic Lymphohistiocytosis
Intervention  ICMJE 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 p.o.bid + 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
Study Arms  ICMJE 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.
Intervention: Drug: IST and/or alloHCT
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 22, 2016)
12
Original Estimated Enrollment  ICMJE
 (submitted: March 3, 2012)
50
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date May 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01547143
Other Study ID Numbers  ICMJE AMC-H-72
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dae-Young Kim, Asan Medical Center
Study Sponsor  ICMJE Asan Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dae-Young Kim, MD Asan Medical Center
PRS Account Asan Medical Center
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP