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

Open (Enrolling)
Gastric Cancer, Leukemia, Chronic Myelogenous Leukemia

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Trial Information

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

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.

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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Outcome Measure:

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).

Outcome Time Frame:

Every 3 months (+2 weeks)

Safety Issue:


Principal Investigator

Ellin Berman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2006

Completion Date:

December 2013

Related Keywords:

  • Gastric Cancer
  • Leukemia
  • Chronic Myelogenous Leukemia
  • Gastric cancer
  • Leukemia
  • Chronic Myelogenous Leukemia
  • Imatinib
  • Gleevec
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Stomach Neoplasms
  • Gastrointestinal Stromal Tumors



Memorial Sloan-Kettering Cancer Center New York, New York  10021