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

Hemophagocytic Lymphohistiocytosis Clinical Trial

— HELA2012  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01547143
• Other study ID #: AMC-H-72
• Status: Terminated
• Phase: N/A
• Start date: March 2012
• Est. completion date: May 2016

Study information

• Verified date: July 2018
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Intervention

Drug:
• IST and/or alloHCT
1) Patients will be categorized by their initial serum ferritin level. Mild ( ferritin<3,000 µg/L): close observation Moderate (ferritin: 3,000-10,000 µg/L): Initiation : cyclosporine 3mg/kg p.o.bid + dexamethasone 10mg/m2/d po. or i.v. (D1-3) continuation: cyclosporine 3mg/kg p.o. bid (D4-56) + dexamethasone 10mg/m2/d (D4-14), then tapering. Severe (ferritin>10,000 µg/L): initiation : etoposide 100mg/m2/d i.v. + cyclosporine 2mg/kg i.v. q 12hours + dexamethasone 20mg/m2/d i.v. (D1-3) 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.

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical center, University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (47)

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* Note: There are 47 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival rate		1-year
Secondary	Complete response rate		28 days
Secondary	Complete response rate		56 days
Secondary	Complete response rate		3 months
Secondary	Partial response rate		28 days
Secondary	Partial response rate		56 days
Secondary	Partial response rate		3 months
Secondary	reactivation-free survival rate		3 months
Secondary	reactivation-free survival rate		6 months
Secondary	overall survival rate		3 months
Secondary	overall survival rate		6 months
Secondary	overall survival rate		1 year
Secondary	treatment-related mortality rate		1 year