Clinical Trial: Imatinib in KIT-negative Systemic Mastocytosis
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations
Brief Summary: The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Imatinib Mesylate therapy in patients with systemic mastocytosis lacking KIT mutations.
Detailed Summary:
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 followi
Sponsor: Hospital Virgen de la Salud
Current Primary Outcome:
- To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration. [ Time Frame: 6 months ]The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients with B or C findings
- To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration. [ Time Frame: 12 months ]The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients without B or C findings, and from those with B or C findings who show response at the intermediate check-point (after 6 months of therapy)
Original Primary Outcome: 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. [ Time Frame: 12 months ]
Current Secondary Outcome:
- To evaluate the effect of Imatinib Mesylate on mastocytosis skin lesions. [ Time Frame: 12 months ]Skin lesions are evaluated before and after therapy by macroscopic examination and skin biopsy.
- To evaluate the effect of Imatinib Mesylate on mastocytosis mast-cell related symptoms. [ Time Frame: 12 months ]Clinical symptoms such as pruritus, flushing, gastrointestinal symptoms and anaphylaxis are assessed before and after therapy using a clinical questionnaire that includes the type, frequency and severity of each symptom.
- To evaluate the effect of Imatinib Mesylate on mastocytosis-related megalies. [ Time Frame: 12 months ]Organomegalies and adenomegalies are assessed before and after therapy by abdominal ultrasound.
- To evaluate the effect of Imatinib Mesylate on mastocytosis-related bone alterations. [ Time Frame: 12 months ]Bone alterations are assessed before and after therapy by X-ray survey.
- To investigate changes after Imatinib Mesilate therapy in mast cell clonality. [ Time Frame: 12 months ]Genetic abnormalities are assessed before and after therapy by sequencyng analysis of the c-kit gene and the HUMARA assay.
- To determine the effect of Imatinib Mesylate therapy on serum tryptase levels. [ Time Frame: 12 months ]Serum tryptase is measured before and after therapy.
- To determine the effect of Imatinib Mesylate therapy in the psychological impact of the disease and the quality of life. [ Time Frame: 12 months ]The psychological impact of the disease and the quality of life of patients are evaluated before and after therapy by the Dermatology Life Quality Index.
Original Secondary Outcome:
- To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration as assessed by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells. [ Time Frame: 12 months ]
- To investigate changes after Imatinib Mesilate therapy in mast cell clonality as assessed by the HUMARA test performed on highly-purified bone marrow mast cells. [ Time Frame: 12 months ]
- To determine the effect of Imatinib Mesylate therapy on serum tryptase levels. [ Time Frame: 12 months ]
- To determine the effect of Imatinib Mesylate therapy in the psychological impact of the disease and the quality of life of patients as assessed by the Dermatology Life Quality Index . [ Time Frame: 12 months ]
Information By: Hospital Virgen de la Salud
Dates:
Date Received: February 16, 2011
Date Started: January 2011
Date Completion:
Last Updated: August 26, 2016
Last Verified: August 2016
