E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a phase II, multi-center study of pomalidomide in adult patients with Primary myelofibrosis, Secondary myelofibrosis, and unclassifiable Myeloproliferative Neoplasms showing at least grade 1 bone marrow fibrosis and requiring therapy. |
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E.1.1.1 | Medical condition in easily understood language |
multi-center,phase II study of pomalidomide in adult patients with Primary MF, Secondary MF, and unclassifiable MPN showing at least grade 1 bone marrow fibrosis and requiring therapy. |
Multizentrische Phase II-Studie mit Pomalidomid bei Patienten mit myeloproliferativer Neoplasie und Knochenmarkfibrose |
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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 clinical efficacy (disease response) of pomalidomide in MF patients based on the consensus criteria of the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT), extended by the criterion RBC-transfusion independence (TI) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety profile of pomalidomide in MF patients • To assess predictive response parameters using cytogenetic and molecular genetic analyses including microarray-based techniques • To assess overall clinical outcome
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥50 years at the time of voluntarily signing an IRB/IEC-approved informed consent 2. Diagnosis of Myeloproliferative Neoplasms (MPN) either de novo myelofibrosis according to WHO criteria (PMF), secondary myelofibrosis (post-PV MF and post-ET MF according to the IWG-MRT consensus terminology) or unclassifiable MPN with biopsy proven myelofibrosis 3. Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia and/or thrombocytopenia <50 /nl or transfusion-dependent thrombocytopenia and/or neutropenia <1.0 /nl 4. Splenomegaly (>11 cm diameter) and/or leukoerythroblastosis 5. Adequate organ function, i.e. ALT and/or AST <3 x upper limit of normal (ULN), total bilirubin <3 x ULN, and serum creatinine <2 mg/dl 6. Subject must be willing to receive transfusion of blood products 7. ECOG performance status <3 8. Female subjects with non-childbearing potential°, - Must have one medically supervised negative serum or urine pregnancy tests prior to starting study drug. 9. Male subjects - must agree to use condoms throughout study drug therapy, during any dose interruption and for four weeks after cessation of study therapy if their partner is of childbearing potential and has no contraception - even if they have undergone a successful vasectomy. - must agree not to donate semen during study drug therapy and for 90 days following discontinuation of pomalidomide. 10. All Subjects (males and females) - Will be counseled about potential teratogenic risks of the study medication. - must agree to abstain from donating blood while taking study drug therapy and for at least 28 days following discontinuation of pomalidomide. - must agree not to share study medication with another person and to return all unused study drug to the investigator - Only enough pomalidomide for one cycle of therapy may be dispensed with each cycle of therapy.
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E.4 | Principal exclusion criteria |
1. Females of childbearing potentials, pregnant or breast feeding females 2. BCR/ABL-positivity 3. Diagnosis of ET (according to WHO 2008 criteria) 4. Diagnosis of PV (according to WHO 2008 criteria) 5. >20% blasts in peripheral blood or bone marrow 6. Known positive status for HIV, HBV or HCV 7. Prior treatment with IMiDs (thalidomide, lenalidomide) or with Interferon-alpha within a 3 month time period before screening 8. History of thrombosis or pulmonary embolism 9. Peripheral neuropathy >grade 1 CTC 10. No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation. 11. Presence of any medical/psychiatric condition or laboratory abnormalities which may limit full compliance with the study, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study 12. Drug or alcohol abuse within the last 6 months 13. Patients with a “currently active” second malignancy other than non-melanoma skin cancers. Patients are not considered to have a “currently active” malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective disease response, as defined by the IWG-MRT criteria for response in MF patients,extended by the criterion RBC-transfusion independence (TI) |
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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) |
• Overall safety profile of pomalidomide characterized by type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during treatment • Event-free, relapse-free and overall survival
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety will be monitored by internal and external supervision. After cohorts of 38 patients,the analyses of the safety end points was performed.
Twelve-monthly, a study report comprising the safety end point report, a summary as well as a complete list of serious adverse events (SAE), results of blinded central versus on-site disease assessment and a summary of study conduct to assess protocol adherence will be performed. |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
predictive response parameters using cytogenetic and molecular genetic analyses including microarray |
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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 | No |
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.8.3 |
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 | 15 |
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 | No |
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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patient remain on treatm until PD for at least 12 cycles, withdrawal of IC or the occurrence of unaccepted toxicity conditions leading to patient withdrawal from the study are detailed in the protcol.If a patient may benefit from treatm the possibility of further treatm including maintenance treatm with pomalidomide on a case-by-case decision will be discussed. This additionell treatm will be performed within the FU period of the study, data will be collected and duration will be max. 12 cycles |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |