E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic myeloid neoplasms
Essential thrombocythemia
Polycythemia vera
primary myelofibrosis |
Kroniske myeloide neoplasier
Essential thrombocythemia
Polycythemia vera
primary myelofibrosis |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic myeloid neoplasms
Essential thrombocythemia
Polycythemia vera
primary myelofibrosis |
Kroniske myeloide neoplasier
Essential thrombocythemia
Polycythemia vera
primary myelofibrosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 |
To evaluate hematological and molecular response in danish patients with Ph-negative chronic myeloid neoplasms (CMPN); Essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) treated with low-dose interferon-alpha (IFN-alpha)(Pegasys and PegIntron) and Hydrea.
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At sammenligne behandlingseffekt, klinisk og molekylært hos danske patienter med Ph-negative kroniske myeloide neoplasier (CMPN); essential trombocytose (ET), polycytæmia vera (PV) og primær myelofibrose (PMF) i behandling med lav-dosis Interferon Alpha (IFN-alpha) (Pegasys og PegIntron) og Hydrea. |
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E.2.2 | Secondary objectives of the trial |
1. To investigate and compare the toxicity of Pegasys and PegIntron and
Hydrea.
2. To investigate quality of life among danish patients treated with
Pegasys, PegIntron, and Hydrea.
3. To investigate the occurence of neutralizing antibodies against
Pegasys and PegIntron.
4. To investigate the histopathological response in the bone marrow
during treatment with low-dose interferon-alpha (IFN-alpha)(Pegasys,
PegIntron) and Hydrea.
5. To investigate the sustainability of an obtained molecular remission (<
1% JAK2V617F mutated alleles) after discontinuation of interferon-
alpha( Pegasys or PegIntron) or Hydrea.
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1. At undersøge toksiciteten af Pegasys og PegIntron, dels de to præparater imellem, men også overfor Hydrea.
2. At undersøge livskvaliteten hos danske patienter i behandling med Pegasys, PegIntron og Hydrea.
3.At undersøge forekomsten af neutraliserende interferon antistoffer hos patienter i behandling med Pegasys og PegIntron.
4.At undersøge det histopatologiske respons i knoglemarven under pågående behandling med lav-dosis Interferon Alpha (IFN-alpha) (Pegasys og PegIntron) og Hydrea.
5. At undersøge varigheden af behandlingsinduceret dyb molekylærbiologisk remission hos JAK2 V617F muterede CMPN patienter (< 1% JAK2V617F muterede alleler), efter ophør af behandling med IFN-alpha ( Pegasys og PegIntron) og Hydrea.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female > 18 years of age
2.Newly diagnosed or previously untreated patients with ET, PV or PMF including prefibrotic
myelofibrosis according to the WHO classification
3.Active disease defined by one of the following criteria:
- need for phlebotomy
- leukocytosis > 10 mia/l
- thrombocytosis > 400 mia/l
- constitutional symptoms (fatigue, weight loss, night sweats or
fewer > 38 degrees celsius)
- Pruritus
- splenomegali causing symptoms
- previous thrombosis
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1.Mandlig eller kvindelig patient > 18 år.
2.Nydiagnosticerede eller tidligere ubehandlede patienter med ET, PV eller proliferativ PMF
inklusiv prefibrotisk myelofibrose i henhold til WHO klassifikationen.
3.Aktiv sygdom defineret ved ét eller flere af følgende kriterier:
- Behov for venesektio ( Htc > 0,42 kvinder, > 0,45 mænd)
- Leukocyttal > 10 mia/l ved fravær af infektion/inflammation.
- Trombocyttal > 400 mia/l ved fravær infektion/inflammation.
- Hypermetabole symptomer (træthed, vægttab, nattesved og
subfebrilia)
- Pruitus
- Symptomgivende splenomegali
- Forekomst af tidligere trombose
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E.4 | Principal exclusion criteria |
-Fertile women without a negative pregnancy test
-Other malignant disease within last 5 yaers
-ECOG performance score >/= 3
-Creatinine > 2x ULN
-Bilirubin > 1.5x ULN
-ALAT > 3x ULN
-Previous psyciatric disorder (depression)
-active autoimmune disease
-Uncontrolled thyroid disease |
-Fødedygtige patienter uden en negativ graviditetstest inden
igangsættelse af undersøgelseslægemiddel.
- Anden aktiv malign sygdom indenfor de seneste 5 år.
- ECOG-funktionsscore >/= 3
- Serum kreatinin mere end 2 x ULN
- Total serum bilirubin mere end 1,5 x ULN
- Plasma ALAT mere end 3 x ULN
- Tidligere psykiatrisk lidelse (depression).
- Autoimmun sygdom.
- Ukontrolleret stofskifte sygdom.
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E.5 End points |
E.5.1 | Primary end point(s) |
Molecular response (JAK2 V617F allele burden) assesed by qPCR according to ELN criteria (changes from baseline). |
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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) |
1. Hematological response, (complete and partial) according to ELN
criteria for ET and PV and EUMNET criteria for PMF.
2. Toxicity (discontinuation of PegIntron, Pegasys og Hydrea due to
intolerability).
3. Quality of life (changes from baseline).
4. Histopathological response (changes from baseline).
5. Sustained molecular response (changes from level at time of
discontinuation of therapy).
6. Neutralizing antibodies against PegIntron and Pegasys |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 12 months
2. 18 months
3. 4, 12, 24, 36, 48 and 60 months.
4. 36 and 60 months.
5. From time point of discontinuation of therapy and every 4. months.
6. 24 months |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | No |
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 | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |