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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000407-20 | EudraCT Number |
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| Name | Class |
|---|---|
| Incyte Corporation | INDUSTRY |
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This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs)
This project aims to test the effectiveness of ITACITINIB in sporadic Hemophagocytosis Lymphohistiocytosis (HLHs). The existence of an IFN-γ signature, in HLHs, is a strong rational for testing the use of a JAK1 inhibitor in the treatment of HLHs. We hypothesize that ITACITINIB, an inhibitor of JAK-1, may be a therapeutic of interest in the treatment of non-severe HLHs in replacement of corticosteroids by inhibiting the production and effects of IFN-γ but also those of other pro-inflammatory cytokines. The use JAK-1 inhibitor instead of corticosteroids in patients with HLHs without any sign of severity is justified by its probable lesser toxicity and higher efficiency.
In this proof of concept study, because of the vital risk associated with severe HLH and the efficacy of Etoposide in this setting, we will first include only patients with moderate HLHs
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment arm | Experimental | 300 mg of ITACITINIB will be administrated per os every day for 30 days, dose with reduction to 200 mg per safety is allowed if AEs are observed or if co-administered a strong CYP3A inhibitor |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Itacitinib | Drug | Administration of 300 mg of ITACITINIB per os every day for 30 days. |
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| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of ITACITINIB | Efficacy at day 15 of ITACITINIB treatment in non-severe adults HLH | At day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Response rate of ITACITINIB at D8 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria | Response rate at D8 of treatment | day 8 |
| Efficacy at the day of etiologic treatment if patients received at least 7 days of treatment (ITACITINIB taken until J15) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Avicenne | Bobigny | Bobigny | 93000 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15661029 | Result | Menasche G, Feldmann J, Fischer A, de Saint Basile G. Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis. Immunol Rev. 2005 Feb;203:165-79. doi: 10.1111/j.0105-2896.2005.00224.x. | |
| 20049711 | Result | Pachlopnik Schmid J, Ho CH, Chretien F, Lefebvre JM, Pivert G, Kosco-Vilbois M, Ferlin W, Geissmann F, Fischer A, de Saint Basile G. Neutralization of IFNgamma defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice. EMBO Mol Med. 2009 May;1(2):112-24. doi: 10.1002/emmm.200900009. |
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| ID | Term |
|---|---|
| C000718170 | itacitinib |
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Rate of complete response to ITACITINIB treatment for HLHs in adults without any sign of severity at the day of etiologic treatment if patients have been treated by ITACITINIB at least during seven days. Response to ITACITINIB is evaluated at the day of etiologic treatment on the major and minor diagnostic criteria of HLH |
| At day 15 |
| Toxicity of ITACITINIB | Toxicity of ITACITINIB not related to evolution of HLH (cytopenia, worsening of hepatic balance, secondary infections) | 21 months |
| Rescue therapy | In the case of worsening, treatment will be stopped and switch for HLH specific treatment as VP16, (etoposide) | 21 months |
| Reduction of plasma cytokines level between D0 and D15 and correlation to the therapeutic response to D15 | Range of decrease in plasma rate of IFN-Gamma, IP-10, Il-1, Il-6, IL-10, TNF-alpha, between D0 and D15 of ITACITINIB treatment in each patient group: response and progression | At day 15 |
| Clinical, biological, associated diseases characteristics of patients having CR, PR, Progression | Clinical, biological, associated diseases and evolutions characteristics of patients in each response | 21 months |
| Overall survival at 3 | Overall survival at 3 | 3 months |
| Response rate of ITACITINIB at D30 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria | Response rate at D30 of treatment | day 30 |
| Response rate of ITACITINIB at D90 on clinical and biological symptoms of primitive/refractory/relapse adults HLHs without severity criteria | Response rate at D90 of treatment | day 90 |
| 15466922 | Result | Billiau AD, Roskams T, Van Damme-Lombaerts R, Matthys P, Wouters C. Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-gamma-producing lymphocytes and IL-6- and TNF-alpha-producing macrophages. Blood. 2005 Feb 15;105(4):1648-51. doi: 10.1182/blood-2004-08-2997. Epub 2004 Oct 5. |
| 22869151 | Result | Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene. 2013 May 23;32(21):2601-13. doi: 10.1038/onc.2012.347. Epub 2012 Aug 6. |
| 27222478 | Result | Maschalidi S, Sepulveda FE, Garrigue A, Fischer A, de Saint Basile G. Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood. 2016 Jul 7;128(1):60-71. doi: 10.1182/blood-2016-02-700013. Epub 2016 May 24. |