MedDRA version: 18.1 Level: LLT Classification code 10028538 Term: Myelofibrosis with myelometaplasia System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10036061 Term: Polycythemia vera System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10053134 Term: Osteomyelofibrosis System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Jakavi
Product Name: Jakavi
Pharmaceutical Form: Tablet
Other descriptive name: RUXOLITINIB
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 10-40
Trad
Sponsors
Roskilde University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 3.1 Inclusion Criteria 1. Male or female patients> 18 years. 2. Patients with early prefibrotic myelofibrosis /post-ET myelofibrosis , PV, Post-PV myelofibrosis or hyperproliferative PMF according to WHO classification. 3. Active disease defined by one or more of the following criteria, at some time before study enrollment and accordingly not necessarily at the time or weeks before enrollment : a) Need for venesection (hematocrit> 0.42 in females and > 0.45 in males) b) White blood cell counts > 10 MIA/L in the absence of infection / inflammation. c) Platelet count> 400 MIA/L in the absence infection / inflammation. d) Hypermetabolic symptoms such as weight loss (> 10% within 6 months), night sweats and subfebrilia (temperature> 38 º C for more than 2 weeks without signs of infection) e) Pruritus f) Symptomatic splenomegaly g) Presence of previous thrombosis. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 3.2 Exclusion Criteria 1. Childbearing potential patients without a negative pregnancy test prior to initiation of study drug and / or non-acceptance of the use of effective contraceptive methods * 2. Other active malignancy within the past 5 years (except basal cell carcinoma of the skin). 3. ECOG function scores> / = 3 4. Serum creatinine more than 2 x ULN 5. Total serum bilirubin greater than 1.5 x ULN 6. Plasma ALT more than 3 x ULN 7. Former psychiatric disorder (depression diagnosed by a psychiatrist) 8. Uncontrolled metabolic disease. 9. Severe heart disease (heart failure NYHA class 3-4). 10. Severe myelosuppression. (leucocyte count<1.5 Mill/L, Platelet count<100) 11. Chronic hepatitis with decompensated cirrhosis. 12. Chronic hepatitis in patients who have been or recently (within 6 months) has been treated with immunosuppressive drugs with the exception of corticosteroid treatment. 13. Epilepsy and / or other serious CNS disorders. 14. Known hypersensitivity to recombinant interferon (Pegasys or PegIntron) and JAKAVI, or to one or more of these preparations . * Spiral, birth control pills, implants, transdermal patch, vaginal ring or transdermal injection. Sterile / infertile subjects are exempt from the use of contraception. In order to be considered sterile or infertile, one must generally be surgically sterilized (vasectomy, bilateral tubectomy, hysterectomy or ovariectomy) or be postmenopausal, defined as absent menstruation for at least 12 months before study enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objectives 1. To describe the effect of combination therapy with IFN-alpha (Pegasys, PegIntron) and JAK1-2-inhibitor treatment (ruxolitinib) evaluated by hematological parameters (Hb, hematocrit, white blood cell count, platelet count, LDH, reduction in JAK2V617-mutation allele burden) and quality of life score, which indirectly will also reflect the remission of the IFN-alpha-induced side effects ;Secondary Objective: Secondary Objectives 1. To investigate whether additional treatment with JAK1-2-inhibitor (ruxolitinib) to patients who show intolerance (due to adverse events) during treatment with interferon-alpha (IFN-alpha) (Pegasys, PegIntron) can improve the efficacy based on individual contribution of the two agents regarding that the JAK1-2 inhibitor through its very potent anti-inflammatory efficacy profile may dampen the impact of the systemic inflammatory response mediated by IFN-alpha. ;Timepoint(s) of evaluation of this end point: Study end (LPLV): February 2019;Primary end point(s): ENDPOINTS Objective Endpoint related to objective To describe the effect of combination therapy with IFN-alpha (Pegasys, PegIntron) and JAK1-2-inhibitor treatment (ruxolitinib) Change in hematological parameters (Hb, hematocrit, white blood cell count, platelet count, LDH, reduction in JAK2V617-mutation allele burden) and Change in quality of life score from baseline (MPN-SAF) To investigate whether additional treatment with JAK1-2-inhibitor (ruxolitinib) to patients who show intolerance (due to adverse events) during treatment with interferon-alpha (IFN-alpha) (Pegasys, PegIntron) can improve the efficacy based on individual contribution of the two agents regarding that the JAK1-2 inhibitor through its very potent anti-inflammatory effect profile may dampen the systemic inflammatory response mediated by IFN-alpha. Difference in number of IFN-related adverse events compared to matched group in the Dahlia study The compliance to the treatmen | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ENDPOINTS Objective Endpoint related to objective To describe the effect of combination therapy with IFN-alpha (Pegasys, PegIntron) and JAK1-2-inhibitor treatment (ruxolitinib) Change in hematological parameters (Hb, hematocrit, white blood cell count, platelet count, LDH, reduction in JAK2V617-mutation allele burden) and Change in quality of life score from baseline (MPN-SAF) To investigate whether additional treatment with JAK1-2-inhibitor (ruxolitinib) to patients who show intolerance (due to adverse events) during treatment with interferon-alpha (IFN-alpha) (Pegasys, PegIntron) can improve the efficacy based on individual contribution of the two agents regarding that the JAK1-2 inhibitor through its very potent anti-inflammatory effect profile may dampen the systemic inflammatory response mediated by IFN-alpha. Difference in number of IFN-related adverse events compared to matched group in the Dahlia study The compliance to the treatment, as measured by the number of patients who discontinue ruxolitinib/IFN for AE, and the safety of the treatment, as measured by the number and the type of SAE during Ruxolitinib/IFN alpha treatment. To investigate whether additional treatment with JAK1-2-inhibitor (ruxolitinib) to patients who exhibit lack of efficacy of treatment (IFN-alpha) (Pegasys, PegIntron) can establish / re-establish treatment response regarding that the JAK1-2 inhibitor through its very potent anti-inflammatory effect profile may reduce / eliminate the systemic inflammation response - mediated by IFN-alpha and MPN disease per se – and thereby potentially may facilitate the inhibition of clonal expansion (by down-regulation of inflammatory cytokines - TNF-alpha 2, IL-6 etc. - and perhaps through an enhancement of IFN-alpha's effects on the immune cells of interest for intact "Tumor Immune Surveillance "(for example, NK cells, dendritic cells, cytotoxic T cells, regulatory T cells) Number of patients with complete | — |
Countries
Denmark
Contacts
Public ContactMads Emil Bjørn
Roskilde Hospital
Outcome results
None listed