A prospective multicentre phase II trial of zoledronic acid in patients with myelofibrosis with myeloid metaplasia (MMM) - zoledronic acid in myelofibrosis
- Conditions
- myelofibrosis with myeloid metaplasia
- Registration Number
- EUCTR2005-003985-40-BE
- Lead Sponsor
- Department of Internal Medicine, University Hospital Gasthuisberg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 16
?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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
?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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: to assess the efficacy and safety of zoledronic acid in patients with myelofibrosis;Secondary Objective: The secondary objectives of this study are to evaluate in patients with myelofibrosis the effect of Zometa® on:<br><br>?red blood cell transfusion need<br><br>?performance status and constitutional symptoms<br><br>? leukocyte/thrombocyte count <br><br>?bone marrow histology, i.e. reticulin fibrosis, collagen fibrosis, osteosclerosis and angiogenesis <br><br>?serum LDH<br><br>?cytogenetics i.e. clonal evolution or regression<br><br>?bone remodelling<br>;Primary end point(s): The primary objectives of this study are to evaluate in patients with myelofibrosis:<br><br>?the effect of Zometa® on hemoglobin level <br><br>?the effect of Zometa® acid on spleen size<br><br>?the safety of Zometa®<br>
- Secondary Outcome Measures
Name Time Method