early and fibrotic stages of primary myelofibrosis MedDRA version: 14.1 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Multiferon
Pharmaceutical Form: Solution for injection in pre-filled syringe
Sponsors
The Nordic Myeloproliferative Neoplasm Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: – Patients fulfilling WHO criteria for early-PMF (primary myelofibrosis) or fibrotic-PMF – Bone marrow fibrosis grades MF-1 or MF-2 (diagnosis should be confirmed by adjudication panel) – Men and women 18-75 years – Signed and dated written informed consent 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: – Presence of extensive fibrosis, i.e MF-3 – Presence of the following symptoms and/or abnormal parameters: • Constitutional symptoms (weight loss > 10% of the baseline value in the year preceding PMF diagnosis and/or unexplained fever or excessive sweats persisting for more than one month) • Splenomegaly (palpable or excessive > 5 cm and /or painful splenomegaly) • Hb 1000*10e9/L • Intermediate-2 or high risk PMF – Previous therapy for Myeloproliferative Neoplasm including hydroxyurea, interferon or anagralide during the last 6 months or has received any of these medications for more than 6 months during the last 2 years. - Myelofibrosis secondary to other MPN: • Patients who fulfils WHO criteria for Polycytemia Vera and/or have been treated with phlebotomy. • Patients having (known) thrombocytosis for more than 5 years unless BM biopsy at time of diagnosis confirms the presence of PF-MF – Contraindication to interferon treatment: • Significant hepatic dysfunction: AST, ALT >40 U/l; • Significant renal dysfunction: serum creatinine >150 umol/l; • History of psychiatric disorder; • Autoimmune hepatitis; • Chronic hepatitis with liver cirrhosis; • Severe cardiac dysfunction; • Known hypersensitivity to IFN; • existing hypo- or hyperthyroidism; • epilepsy. – Pregnancy or breast feeding women; – Unable or unwilling to sign consent; – Expected survival <3 years; – Presence of active malignant disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the efficacy of Multiferon in untreated patients with low/intermediate-1 risk early-PMF (primary myelofibrosis) or fibrotic-PMF. The efficacy will be assessed by the proportion of patients who shows regression in the grade of bone marrow fibrosis and/or restoration of cellular changes. ;Secondary Objective: - To determine the safety and tolerability of Multiferon - Determine the rate of progression/regression of fiber density. - To determine the effect of treatment on clinical and hematological parameters. - To determine the rate of clinical progression (development of symptomatic MF or leukemic transformation). - To assess the effect of treatment on JAK -2 allele burden. - To assess the effect of treatment on HRQoL. -spin-off studies;Primary end point(s): The proportion of patients with regressing fibrosis and/or normalization of bone marrow cellularity and megakaryocyte abnormalities at one and two year follow-up.;Timepoint(s) of evaluation of this end point: Year 1 and year 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main secondary endpoints: – More than grade 2 adverse events. – Discontinuation of treatment because of intolerance. Other Secondary endpoints: – The development of PMF with fibrosis grade MF-3 – Development of symptomatic PMF: • clinical (splenomegaly, constitutional symptoms) • hematological parameters (anemia, thrombocytopenia ) – JAK2 allele burden – HR-QoL – Transformation to acute myeloid leukemias – Arterial and venous thrombosis – Death ;Timepoint(s) of evaluation of this end point: Year 1 and year 2 | — |
Countries
Norway
Contacts
Public ContactWaleed Ghanima
The Nordic Myeloproliferative Neoplasm Group
Outcome results
None listed