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

This study is currently recruiting participants.
Verified January 2013 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Dae-Young Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01547143
First received: February 29, 2012
Last updated: January 3, 2013
Last verified: January 2013
History of Changes
  Purpose

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: IHT and alloHCT

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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:

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • overall survival rate [ Time Frame: 1-year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Partial response rate [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Partial response rate [ Time Frame: 56 days ] [ Designated as safety issue: No ]
  • Partial response rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • reactivation-free survival rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • reactivation-free survival rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • overall survival rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • overall survival rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • overall survival rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • treatment-related mortality rate [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: March 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm
Patients who are newly diagnosed as HLH by HLH-2004 criteria, excluding those with HLH owing to malignancy or rheumatic disorder.
 Drug: IHT and alloHCT

1) Patients who enroll this trial will be categorized into 3 groups by their initial serum ferritin level.

  1. Mild ( ferritin<3,000 μg/L): close observation with routine check-up

  2. Moderate (ferritin: 3,000-10,000 μg/L):

    1. Initiation therapy: cyclosporine 3mg/kg p.o.bid + dexamethasone 10mg/m2/d po. or i.v. (D1-3)
    2. continuation therapy: cyclosporine 3mg/kg p.o. bid (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.

  3. Severe (ferritin>10,000 μg/L):

    1. initiation therapy: etoposide 100mg/m2/d i.v. + cyclosporine 2mg/kg i.v. q 12hours + dexamethasone 20mg/m2/d i.v. (D1-3)

    2. continuation therapy: 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 can be performed for refractory or reactivated cases.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01547143

Contacts
Contact: Hye Jeong Park, RN 82-2-3010-7290 peechss@naver.com

Locations
Korea, Republic of
Asan Medical center, University of Ulsan College of Medicine Recruiting
Seoul, Korea, Republic of
Contact: Hye Jeong Park, RN     82-2-3010-7290     peechss@naver.com    
Principal Investigator: Dae-Young Kim, MD            
Sub-Investigator: Kyoo-Hyung Lee, MD, PhD            
Sub-Investigator: Je-Hwan Lee, MD, PhD            
Sub-Investigator: Jung-Hee Lee, MD, PhD            
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Dae-Young Kim, MD Asan Medical Center
  More Information

Publications:

Responsible Party: Dae-Young Kim, Assistant Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01547143     History of Changes
Other Study ID Numbers: AMC-H-72
Study First Received: February 29, 2012
Last Updated: January 3, 2013
Health Authority: South Korea: Institutional Review Board

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

Additional relevant MeSH terms:
Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases
Etoposide
 Etoposide phosphate
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013