A Trial of Zoledronic Acid in Patients With Myelofibrosis With Myeloid Metaplasia (MMM)

Myelofibrosis Clinical Trial

Official title:

A Prospective Multicentre Phase II Trial of Zoledronic Acid in Patients With Myelofibrosis With Myeloid Metaplasia (MMM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00287261
• Other study ID #: CZOL446G2422
• Status: Completed
• Phase: Phase 2
• First received: February 2, 2006
• Last updated: December 8, 2014
• Start date: February 2006
• Est. completion date: March 2008

Study information

• Verified date: December 2014
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP
• Study type: Interventional

Clinical Trial Summary

In this trial, the question is addressed if zoledronic acid (Zometa, Novartis Pharma)could be of clinical benefit for patients with myelofibrosis and myeloid metaplasia (MMM).

Description:

This is a prospective, multicentre phase II study in adult patients with documented MMM and requiring therapy for their disease. Patients will be treated every 3 weeks with 4 mg zoledronic acid (Zometa), administered by a 15 min. intravenous infusion. Study duration is 36 weeks (12 infusions). After the study it is recommended to continue treatment until disease progression, or the occurrence of unacceptable treatment-related toxicity.

Objectives of the trial are:

Primary objectives: the effect of monthly infusion of zoledronic acid 4 mg on:

hemoglobin level, spleen size

Secondary objectives the effect of monthly infusion of zoledronic acid 4 mg on: red blood cell transfusion need performance status constitutional symptoms leukocyte count thrombocyte count bone marrow fibrosis serum LDH

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (following the Dupriez score) may be included 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

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metaplasia
• Myelofibrosis
• Myeloid Metaplasia
• Primary Myelofibrosis

Intervention

Drug:
• zoledronic acid
4 mg IV every 3 weeks for 36 weeks

Locations

Country	Name	City	State
Australia	Cancer Care Services	Brisbane	Queensland
Belgium	University Hospital Leuven	Leuven
France	Hopital Avicenne and Paris 13 University	Bobigny
Germany	Medizinische Klinik Kiel	Kiel
Israel	RAMBAM Medical Center and Technion	Haifa
Spain	Hospital Rafael éndez	Murcia	Lorca

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Countries where clinical trial is conducted

Australia,  Belgium,  France,  Germany,  Israel,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect of monthly zoledronic acid infusion on hemoglobin level and spleen size		36 weeks	No
Secondary	red blood cell transfusion need		36 weeks	No
Secondary	performance status		36 weeks	No
Secondary	constitutional symptoms		36 weeks	No
Secondary	leukocyte count		36 weeks	No
Secondary	thrombocyte count		36 weeks	No
Secondary	serum LDH		36 weeks	No
Secondary	bone marrow histology		36 weeks	No
Secondary	safety of zometa infusions		until progression or death	Yes