E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
myelofibrosis with myeloid metaplasia (MMM)
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028538 |
E.1.2 | Term | Myelofibrosis with myelometaplasia |
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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 |
This study is designed to determine the efficacity and safety of three-weekly infusions with zoledronic acid (Zometa) in patients with MMM. The primary objectives of this study are to evaluate in patients with myelofibrosis: - the effect of Zometa on Hemoglobin level - the effect of Zometa on spleen size - the safety of Zometa |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to invaluate in patients with MMM the effect of Zometa on: - red blood cell transfusion need - performans status and constitutional symptoms - leukocyte/thrombocyte count bone marrow histology, i.e reticulin fibrosis, collagen fibrosis, osteosclerosis and angiogenesis - serum LDH - cytogenetics i.e clonal evaluation or regression - bone remodelling |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- written informed consent - at least 18 years-of-age - histologically confirmed diagnosis of MMM (include idiopathic myelofibrosis, polycythemia vera and essential thrombocytemia) - presence of measurable, clinically relevant disease manifestations - ECOG performance status of 0, 1 or 2 - life expectancy of at least 3 months - women of childbearing potential must use a medically acceptable form of contraception during the study and must have a negative urine or serum pregnancy test within 7 days of randomization
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E.4 | Principal exclusion criteria |
- diseases associated with secondary myelofibrosis, such as metastatic carcinoma, lymphoma, myelodisplasia, hairy cell leukemia, mast cell disease, acute leukemia - presence of the chromosomal translocation t(9:22) or molecular BCR/ABL rearrangement - any anti-myelofibrosis drug therapy during the last 4 weeks. This includes chemotherapy, androgens, steroids, thalidomide, hematopoietic growth factors or any other investigational drug - patients that have received biphosphonates in the previous 3 months - known allergy or intolerance to bisphosphonates - abnomal renal function (calculated creatinine clearance < 30mL/min ) - corrected serum calcium < 8.0 mg/dL. - current active dental problems, dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed in the mouth, or of slow healing after dental procedures - patients with nonmalignant conditions wich would confound the evaluation of the primary endpoint, impair tolerance of therapy, or prevent compliance to the protocol including (uncontrolled infections, uncontrolled type 2 Diabetes Mellitus, disease with influence on bone metabolism such as Paget's disease or uncontrolled thyroid or parathyroid dysfunction, cardiovascular, renal, hepatic, pulmonary, and neurologic/psychiatric disease wich would prevend prolonged follow-up) - pregnant or breast feeding females
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E.5 End points |
E.5.1 | Primary end point(s) |
Treatment phase (week 0 to week 36), at each 3 weekly visit: - registration of constitutional symptoms: fever, night sweats, bone pain. - inspection of the mouth - concomitant medication and adverse events - hematology tests - serum biochemistry tests - number of red blood cell transfusions and of platelet transfusions
After 6 Zometa infusions: echography of the upper abdomen
After 12 Zometa infusions: - bone marrow aspirate and bone biopsy - CT scan of the upper abdomen |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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01/10/2009.
The study duration is 36 weeks (or 12 infusions), or until disease progression, or the occurrence of unacceptable treatment-related toxicity |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |