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

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00580281
First received: December 19, 2007
Last updated: October 23, 2013
Last verified: October 2013
  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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Effect of Imatinib on Bone Metabolism in Patients With Chronic Myelogenous Leukemia or Gastrointestinal Stromal Tumors.

Resource links provided by NLM:


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 ]

Enrollment: 33
Study Start Date: November 2006
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: blood, urine, and dexa scan
This study will involve venipuncture for obtaining blood samples; a spot second void (whenever possible) urine sample will be obtained at the same time. A Dexa scan to evaluate bone density will be obtained at the beginning, middle and end of the study.
Other: blood test, urine test, and bone density x-ray.
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00580281     History of Changes
Other Study ID Numbers: 06-142
Study First Received: December 19, 2007
Last Updated: October 23, 2013
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:
Stomach Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Gastrointestinal Stromal Tumors
Leukemia
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014