E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
myelofibrosis with myeloid metaplasia |
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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 assess the efficacy and safety of zoledronic acid in patients with myelofibrosis |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate in patients with myelofibrosis the effect of Zometa® on:
red blood cell transfusion need
performance 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 evolution or regression
bone remodelling
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
male or female and at least 18 years-of-age
histologically confirmed diagnosis of myelofibrosis with myeloid metaplasia (MMM). This includes patients with agnogenic myeloid metaplasia (also known as idiopathic myelofibrosis) and patients with a preceding history of polycythemia vera or essential thrombocytemia (also known as post-polycytemic myelofibrosis). (see Appendix A)
patients with low, intermediate and high risk disease categories may be included. (see Appendix C) - low risk meaning: Hb > 10 g/dl, and WBC between 4 and 30 x 109/l - intermediate risk meaning: Hb < 10 g/dl, or WBC < 4, or > 30 x 109/l - high risk meaning: Hb < 10 g/dl, and WBC < 4 or > 30 x 109/l
presence of measurable, clinically relevant disease manifestations (especially for low risk patients)
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.
written informed consent
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E.4 | Principal exclusion criteria |
diseases associated with secondary myelofibrosis, such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease, acute leukemia (including M7 disease or acute panmyelosis with myelofibrosis)
presence of the chromosomal translocation t(9:22) or molecular BCR/ABL rearrangement as detected by RT-PCR in bone marrow or peripheral blood
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 bisphosphonates in the previous 3 months
known allergy or intolerance to bisphosphonates
abnormal renal function as evidenced by: a calculated creatinine clearance < 30 ml/min (creatinine clearance (CrCl) is calculated using the Cockcroft and Gault formula) (see Appendix F) corrected serum calcium < 8.0 mg/dL . Corrected serum calcium (mg/dl) = measured calcium (mg/dl) + 0.8*[4 – patient serum albumin (g/dl)]
patients with nonmalignant conditions which 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 diseases with influence on bone metabolism such as Paget’s disease or uncontrolled thyroid or parathyroid dysfunction cardiovascular, renal, hepatic, pulmonary and neurologic/psychiatric diseases which would prevent prolonged follow-up
current active dental problems including infection of the teeth or jawbone (maxilla or mandibula); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing after dental procedures
recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)
patients with a history of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
patients treated with any systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days
pregnant or breast feeding females |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objectives of this study are to evaluate in patients with myelofibrosis:
the effect of Zometa® on hemoglobin level
the effect of Zometa® acid on spleen size
the safety of Zometa®
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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 | Information not present in EudraCT |
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 |
translational research (biomarkers) |
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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 | 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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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patients will receive a minimum of 3 infusions and a maximum of 12 infusions of zoledronic acid. Patients will go off study: - in case of progressive disease - when unacceptable toxicity occurs - after 12 infusions for responders |
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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 |