Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis
Schlüsselwörter
Abstrakt
Beschreibung
Hemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder first recognized almost 70 years ago.(1) Genetic and animal studies have indicated that the familial form of HLH is clearly due to a deficiency of cytotoxic killing. Patients with HLH present with a potentially fatal syndrome of 'hyperimmunity.' These patients have severe inflammation, associated with cytopenias and variably severe bone marrow, liver, or CNS damage. Tissue damage and mortality appear to be due to hypercytokinemia related to persistent immune hyperactivation. An animal model of HLH and correlative human studies all suggest that excessive and abnormal activation of T cells drives the pathophysiology of this disorder, and that suppressing this excessive activation is critical for successful therapy of HLH. It is believed a combination of the two proven induction regimens for hemophagocytic lymphohistiocytosis (HLH) (anti-thymocyte globulin (ATG)- and etoposide-based) will result in response rates and overall survival rates at eight weeks which are comparable or better than the current standard of care (induction therapy per the HLH-94 protocol).
Termine
| Zuletzt überprüft: | 10/31/2016 |
| Zuerst eingereicht: | 04/12/2010 |
| Geschätzte Einschreibung eingereicht: | 04/13/2010 |
| Zuerst veröffentlicht: | 04/14/2010 |
| Letztes eingereichtes Update: | 11/14/2016 |
| Letztes Update veröffentlicht: | 11/15/2016 |
| Tatsächliches Startdatum der Studie: | 03/31/2010 |
| Geschätztes primäres Abschlussdatum: | 10/31/2015 |
| Voraussichtliches Abschlussdatum der Studie: | 03/31/2016 |
Zustand oder Krankheit
Intervention / Behandlung
Drug: Induction Therapy
Drug: Induction Therapy
Drug: Induction Therapy
Drug: Induction Therapy
Drug: Induction Therapy
Phase
Armgruppen
| Arm | Intervention / Behandlung |
|---|---|
| Experimental: Induction Therapy ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, >3 yrs: 12/15 mg, on day 7, 14, 21 and 42 | Drug: Induction Therapy ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours). |
Zulassungskriterien
| Studienberechtigte Geschlechter | All |
| Akzeptiert gesunde Freiwillige | Ja |
| Kriterien | Inclusion Criteria: - diagnosis of hemophagocytic lymphohistiocytosis - Patients <18 years of age - The patient must have active disease at the time of enrollment - Patient's legal guardians must sign an Institutional Review Board approved consent form indicating their awareness of the investigational nature and the risks of this study. - Eligible subjects must be enrolled with the protocol coordinating center Exclusion Criteria: - Recent treatment, within 3 months, with another therapeutic regimen for HLH - Known active malignancy - Known rheumatologic diagnosis which may be the underlying cause of HLH - Pregnancy (as determined by serum or urine test) or active breast feeding - Failure to provide signed informed consent |
Ergebnis
Primäre Ergebnismaße
1. Complete Response Rate [8 Weeks]
Sekundäre Ergebnismaße
1. Time to Response [8 Weeks]
2. Overall Survival [8 weeks]
3. Incidence of Infection [8 Weeks or day 180]
4. Incidence and Time to Relapse [8 weeks]
5. Overall Survival to day +100 [8 weeks]
6. Gather Biologic Samples [8 weeks]
