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Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations

Phase 4
18 Years
Open (Enrolling)
Systemic Mastocytosis

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Trial Information

Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations

In vitro studies have proven that imatinib inhibits wild type Kit (wtKit) and suppresses
proliferation of the HMC-1V560G cell line, while it is ineffective on inhibiting the growth
of HMC-1V560G, D816V cells. Apart from wtKit, Kit molecules carrying mutations in the
extracellular, transmembrane and juxtamembrane domains, such as V560G, F522C and K509I,
remain sensitive to imatinib. In contrast, several experiments have provided compelling
evidence regarding the resistance against the growth-inhibitory effects of imatinib on cells
carrying the D816V KIT mutation. As a consequence, sensitive and specific methods should be
used in order to avoid "false" KIT mutation-negative cases and, for that purpose, mainly in
cases with low bone marrow mast cell numbers, mutational studies should be performed using
highly purified bone marrow mast cells by means of Facs sorting systems better than whole
bone marrow, unsorted mononuclear cell fraction or mononuclear cell fraction pre-enriched
using magnetic beads conjugated with anti-CD25 monoclonal antibody. In the present study
mutational studies were performed in all cases in purified bone marrow mast cells (purity >
97%) using a FACSaria system (Becton-Dickinson Biosciences) as previously described.

Patients without B or C findings according to the World Health Organization, and without
features of biological progression of the disease receive oral Imatinib Mesylate 300 mg
daily for up to 12 months or until clinical progression/unacceptable toxicity. Patients with
B or C findings or biological progression initially receive oral Imatinib Mesylate 300 mg
daily for two weeks; then, dose is increased up to 400 mg/day except in patients who develop
hematological or any other dose-limiting toxicity.

Biological progression is defined as the presence of at least one of the following features:
i) increased serum tryptase levels > 200 ng/mL, ii) diffuse bone sclerosis, iii) patchy
sclerosis with osteolysis and increased risk of bone fracture or significant bone pain, and,
iv) organomegalies or lymph node enlargement due to mastocytosis.

Inclusion Criteria:

- Age older than 18 years.

- Diagnosis of systemic mastocytosis in the absence of c-kit mutation.

- ECOG ≤ 3.

- Signed informed consent.

Exclusion Criteria:

- Previous therapy with a tyrosin kinase inhibitor.

- Positive antibodies against HIV or active viral hepatitis.

- Impaired liver function (total bilirubin ≥ 2.0 mg/dl, AST or ALT > 3 x upper limit of

- Impaired renal function (≥ 2.0 mg/dL).

- Grade III-IV cytopenias not related to mastocytosis.

- Severe cardiopathy (grade III/IV of NYHA, or left ventricular ejection fraction <

- Pregnancy or breastfeeding.

- Female patients who do not use contraceptive methods.

Type of Study:


Study Design:

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

Outcome Measure:

To evaluate the effect of Imatinib Mesylate on clinical mastocytosis-related features: skin lesions, mast-cell related symptoms (pruritus, flushing, gastrointestinal symptoms, anaphylaxis), organomegalies/adenopathies and bone alterations.

Outcome Description:

Clinical parameters are evaluated before and after therapy by macroscopic and histological skin examination, the record of frequency and severity of mast cell-mediators release symptoms, abdominal ultrasonography and x-ray survey.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Luis Escribano, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Instituto de Estudios de Mastocitosis de Castilla La Mancha


Spain: Ministry of Health

Study ID:

EudraCT 2010-019189-94



Start Date:

January 2011

Completion Date:

June 2012

Related Keywords:

  • Systemic Mastocytosis
  • Mast cell
  • Mastocytosis
  • Mast cell disease
  • Mastocytosis
  • Urticaria Pigmentosa
  • Mastocytoma
  • Mastocytosis, Systemic