Imatinib in KIT-negative Systemic Mastocytosis

NCT01297777 | Completed Phase 4

• 1 other identifier: EudraCT 2010-019189-94
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Mastocytosis

Keywords

Mast cell; Mastocytosis; Mast cell disease

Outcome Measures

Primary Outcomes (2)

• To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration.

  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

  6 months

• To evaluate the effect of Imatinib Mesylate on the grade of bone marrow mast cells infiltration.

  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)

  12 months

Secondary Outcomes (7)

• To evaluate the effect of Imatinib Mesylate on mastocytosis skin lesions.

  12 months

• To evaluate the effect of Imatinib Mesylate on mastocytosis mast-cell related symptoms.

  12 months

• To evaluate the effect of Imatinib Mesylate on mastocytosis-related megalies.

  12 months

• To evaluate the effect of Imatinib Mesylate on mastocytosis-related bone alterations.

  12 months

• To investigate changes after Imatinib Mesilate therapy in mast cell clonality.

  12 months

Study Arms (1)

Imatinib mesylate

EXPERIMENTAL

Imatinib mesylate 300 or 400 mg daily for 12 months.

Drug: Imatinib Mesylate

Interventions

Imatinib Mesylate DRUG

* In patients without B or C findings and without biological progression: 300 mg/24 h p.o during one year or until progression/unacceptable toxicity. * In patients with B or C findings or biological progression: 300 mg/24 h p.o for two weeks and then 400 mg/24 h p.o for a total of one year of therapy, or until progression/unacceptable toxicity.

Also known as: Gleevec, STI571

Imatinib mesylate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age older than 18 years.
• Diagnosis of systemic mastocytosis in the absence of c-kit mutation.
• ECOG ≤ 3.
• Signed informed consent.

You may not qualify if:

• 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 normal).
• 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 \< 50%).
• Pregnancy or breastfeeding.
• Female patients who do not use contraceptive methods.

Sponsors & Collaborators

• Hospital Virgen de la Salud: lead

Study Sites (1)

Instituto de Estudios de Mastocitosis de Castilla La Mancha; Hospital Virgen del Valle

Toledo, Toledo, 45071, Spain

Location

Related Publications (7)

• Zermati Y, De Sepulveda P, Feger F, Letard S, Kersual J, Casteran N, Gorochov G, Dy M, Ribadeau Dumas A, Dorgham K, Parizot C, Bieche Y, Vidaud M, Lortholary O, Arock M, Hermine O, Dubreuil P. Effect of tyrosine kinase inhibitor STI571 on the kinase activity of wild-type and various mutated c-kit receptors found in mast cell neoplasms. Oncogene. 2003 Feb 6;22(5):660-4. doi: 10.1038/sj.onc.1206120.

  PMID: 12569358 BACKGROUND

• Akin C, Brockow K, D'Ambrosio C, Kirshenbaum AS, Ma Y, Longley BJ, Metcalfe DD. Effects of tyrosine kinase inhibitor STI571 on human mast cells bearing wild-type or mutated c-kit. Exp Hematol. 2003 Aug;31(8):686-92. doi: 10.1016/s0301-472x(03)00112-7.

  PMID: 12901973 BACKGROUND

• Zhang LY, Smith ML, Schultheis B, Fitzgibbon J, Lister TA, Melo JV, Cross NC, Cavenagh JD. A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy. Leuk Res. 2006 Apr;30(4):373-8. doi: 10.1016/j.leukres.2005.08.015. Epub 2005 Sep 22.

  PMID: 16183119 BACKGROUND

• Ma Y, Zeng S, Metcalfe DD, Akin C, Dimitrijevic S, Butterfield JH, McMahon G, Longley BJ. The c-KIT mutation causing human mastocytosis is resistant to STI571 and other KIT kinase inhibitors; kinases with enzymatic site mutations show different inhibitor sensitivity profiles than wild-type kinases and those with regulatory-type mutations. Blood. 2002 Mar 1;99(5):1741-4. doi: 10.1182/blood.v99.5.1741.

  PMID: 11861291 BACKGROUND

• Garcia-Montero AC, Jara-Acevedo M, Teodosio C, Sanchez ML, Nunez R, Prados A, Aldanondo I, Sanchez L, Dominguez M, Botana LM, Sanchez-Jimenez F, Sotlar K, Almeida J, Escribano L, Orfao A. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood. 2006 Oct 1;108(7):2366-72. doi: 10.1182/blood-2006-04-015545. Epub 2006 Jun 1.

  PMID: 16741248 BACKGROUND

• Akin C, Fumo G, Yavuz AS, Lipsky PE, Neckers L, Metcalfe DD. A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood. 2004 Apr 15;103(8):3222-5. doi: 10.1182/blood-2003-11-3816. Epub 2003 Dec 24.

  PMID: 15070706 RESULT

• Hoffmann KM, Moser A, Lohse P, Winkler A, Binder B, Sovinz P, Lackner H, Schwinger W, Benesch M, Urban C. Successful treatment of progressive cutaneous mastocytosis with imatinib in a 2-year-old boy carrying a somatic KIT mutation. Blood. 2008 Sep 1;112(5):1655-7. doi: 10.1182/blood-2008-03-147785. Epub 2008 Jun 20.

  PMID: 18567837 RESULT

MeSH Terms

Conditions

Mastocytosis, Systemic; Mastocytosis; Mast Cell Activation Disorders

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Luis Escribano, MD, PhD

  Instituto de Estudios de Mastocitosis de Castilla La Mancha

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Instituto de Estudios de Mastocitosis de Castilla La Mancha

Study Record Dates

• First Submitted: February 16, 2011
• First Posted: February 17, 2011
• Study Start: January 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 29, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)