Hemophagocytic Lymphohistiocytosis
Conditions
Keywords
Secondary hemophagocytic lymphohistiocytosis of adults
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.
Interventions
DRUGIST 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.
Sponsors
Asan Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall survival rate | 1-year |
Secondary
| Measure | Time frame |
|---|---|
| Complete response rate | 28 days |
| Partial response rate | 28 days |
| reactivation-free survival rate | 3 months |
| overall survival rate | 3 months |
| treatment-related mortality rate | 1 year |
Countries
South Korea
Outcome results
None listed