Effect of Imatinib on Bone Metabolism in Patients With Chronic Myelogenous Leukemia or Gastrointestinal Stromal Tumors - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	Novartis
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00580281

Purpose

The drug that you are taking for your cancer, imatinib (GleevecTM), has recently been shown to have some new types of side effects. In some people, imatinib can affect how bones are made.

The purpose of this study is to find out if imatinib is causing these side effects in you. We can check how your bones form by testing your blood and urine. We can also check your bone strength by doing a special X-ray of your bone called bone density (or DEXA scan).

Condition	Intervention
Gastric Cancer Leukemia Chronic Myelogenous Leukemia	Other: blood test, urine test, and bone density x-ray.

Study Type:	Interventional
Study Design:	Diagnostic, Open Label, Single Group Assignment, Efficacy Study
Official Title:	Effect of Imatinib on Bone Metabolism in Patients With Chronic Myelogenous Leukemia or Gastrointestinal Stromal Tumors.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Stomach Cancer Urine and Urination X-Rays

Drug Information available for: Imatinib Imatinib mesylate

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

This pilot study will collect longitudinal data on bone metabolism for patients treated with imatinib. Sixty patients will be followed over a two-year period on this protocol, with bone marker assessments ascertained every 3 months (+2 weeks). [ Time Frame: Every 3 months (+2 weeks) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	November 2006
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Intervention Details:

start of the study (month 0), and at months 3, 6, 9, 12 (1 year), 15, 18, 21, and 24 (2 years)

Detailed Description:

Preliminary data from this institution suggest that imatinib, likely by inhibiting platelet derived growth factor receptor (PDGFR), inhibits bone formation and resorption in a high percentage of patients with either chronic myelogenous leukemia (CML) or gastrointestinal stromal tumors(GIST).1 Some, but not all, patients taking imatinib developed hypophosphatemia but the effect on bone, as measured by markers of bone synthesis and metabolism, was seen in some patients with normal phosphate levels as well. Marked urinary phosphate wasting with elevated levels of parathyroid hormone was seen in nearly all patients. The effect of imatinib on bone may be dose-related. Patients with hypophosphatemia were routinely started on oral phosphate replacement, but follow up determinations of urinary phosphate wasting were not performed.

The clinical consequences of these abnormalities on bone are not yet known. This trial will study 60 patients with CML in chronic phase, early accelerated phase (as detected by cytogenetics only) or GIST who are already taking imatinib. Parameters relating to bone metabolism will be checked every 3 months for 2 years. We will determine the incidence of bone abnormalities in this treated population, determine whether fasting serum phosphate can predict for changes in bone metabolism, determine whether there is change in bone density by measuring serial bone densitometry, determine whether oral phosphate replacement can restore phosphate balance, and determine whether there is a dose effect of imatinib on parameters of bone metabolism.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with CML in chronic phase, accelerated phase based on cytogenetic abnormalities in addition to Philadelphia chromosome but with less than 5 % blasts, or GIST taking imatinib
Patients with life expectancy of at least 12 months; patients must be on imatinib at time of study entry.
Ability to sign informed consent and/or assent

Exclusion Criteria:

Patients with a known parathyroid disorder; active thyroid disorder except stable, replaced hypothyroidism; Cushing's syndrome; uncontrolled diabetes mellitus (could have unexpected fluid, electrolyte and mineral shifts); sarcoidosis (elevated calcitriol levels from granulomata); hypercalcemia of malignancy (i.e., PTHrP-mediated or extensive bone mets);known tumor-induced osteomalacia; Paget's disease of bone; known X-linged or autosomal dominant hypophosphatemic rickets/osteomalacia; known renal tubular disease (e.g., Fanconi's syndrome); chronic GI malabsorption sydrome.
Patients taking oral calcium in excess of calcium 750 mg and Vitamin D 400 mg daily (ie, that contained in a single multivitamin). Patients taking more than these amounts may be eligible for this study if vitamin and mineral supplementation in excess of this is stopped for a minimum of 2 weeks prior to study entry.
Patients taking oral or intravenous steroids, calcitonin, any selective estrogen modulating agent such as tamoxifen or raloxifene, gallium nitrate, and other bone seeking radionuceotides, any calcimimetic agent such as cinacalet.
Patients who have had prior treatment with cisplatin, carboplatin, oxaliplatin, ifosfamide, or cyclophosphamide.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00580281

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Novartis

Investigators

Principal Investigator:

Ellin Berman, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Ellin Berman, MD )
Study ID Numbers:	06-142
Study First Received:	December 19, 2007
Last Updated:	November 12, 2009
ClinicalTrials.gov Identifier:	NCT00580281 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Gastric cancer
Leukemia
Chronic Myelogenous Leukemia
Imatinib
Gleevec

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Hematologic Diseases
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Protein Kinase Inhibitors
Pharmacologic Actions
Imatinib

Leukemia
Neoplasms
Stomach Diseases
Digestive System Diseases
Neoplasms by Site
Therapeutic Uses
Stomach Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Gastrointestinal Neoplasms
Gastrointestinal Stromal Tumors
Bone Marrow Diseases

ClinicalTrials.gov processed this record on February 08, 2010