E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
early and fibrotic stages of primary myelofibrosis |
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E.1.1.1 | Medical condition in easily understood language |
early and fibrotic stages of primary myelofibrosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028537 |
E.1.2 | Term | Myelofibrosis |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
- 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 < 10 g/dl
• ANC < 1.5 X10e9/L
• Platelet count <100 or >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. |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |