Midostaurin in Indolent Systemic Mastocytosis

NCT ID: NCT01920204

Last Updated: 2015-01-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2015-05-31

Brief Summary

Rationale: Patients with indolent or smoldering systemic mastocytosis can have severe disabling symptoms. Almost all patients have fatigue, a compromised quality of life, hampering normal functioning. Because this form of mastocytosis is not considered life-threatening, mast cell eradication has never been applied and patients receive only symptomatic therapy with histamine blockers. Midostaurin, a c-KIT inhibitor has shown activity regarding symptom control and decrease of malignant mast cells in patients with aggressive systemic mastocytosis (ASM) or mast cell leukemia

Detailed Description

Objective:

Primary: To study in a pilot phase II trial the efficacy of midostaurin administered at an oral dose of 100 mg twice daily in patients with indolent or smoldering systemic mastocytosis on mediator symptom reduction, documented by the Mastocytosis Symptom Assessment Questionnaire, measured at 3 months.

Secondary:

1. To study whether symptom improvement persists at 6 months, and whether midostaurin can reduce mast cell infiltration in the skin and bone marrow, documented by decrease of serum tryptase, decrease of urticaria pigmentosa and decrease of bone marrow mast cells.

2. To assess safety and tolerability of midostaurin in the above mentioned settings

Study design: Single arm, open label pilot phase II study.

Study population: Adult patients (n=20) with histologically documented systemic mastocytosis, indolent or smoldering subtype, with severe symptoms, not controlled by histamine 1 and 2 blockers.

Intervention: treatment with Midostaurin, twice daily 100 mg orally for 6 months continuously.

Conditions

Indolent Systemic Mastocytosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Midostaurin

Treatment with Midostaurin, twice daily 100 mg orally for 6 months continuously.

Group Type: EXPERIMENTAL

Midostaurin,

Intervention Type: DRUG

Midostaurin, twice daily 100 mg orally, continuously for 6 months

Interventions

Midostaurin,

Midostaurin, twice daily 100 mg orally, continuously for 6 months

Intervention Type: DRUG

Other Intervention Names

PKC412

Eligibility Criteria

Inclusion Criteria

• Patients with Indolent Systemic Mastocytosis (ISM) or Smouldering Systemic Mastocytosis (SSM) according to the WHO criteria
• Presence of the D816V c-KIT mutation
• Serum tryptase > 20 mg/l
• Serious mediator-related symptoms that cannot be controlled by H1 and H2 blocking drugs. Symptoms will be scored by an adapted MSAF (mastocytosis symptom assessment form) with at least:

• a pre-study score of 4 or more on 3 non-related items,
• or a pre-study score of 5 or more on 2 non-related items.
• one item from the scoring list can be replaced by flushes 7 or more per week or anaphylactic attacks 1 or more per week.
• Age >18 years
• Willingness to apply optimal contraceptive measures (double barrier method, both men and women) for women below the age of 55, men at all ages; for both: if sexually active.
• Written informed consent

Exclusion Criteria

• Aggressive systemic mastocytosis, mast cell leukemia, or ASM with or without accompanying non-clonal related non-mast cell disorder (SM-ANHMD).
• Any known other present malignancy, non-melanoma skin cancers excluded
• History of malignancy within the last 5 years, non-melanoma skin cancers excluded
• Any serious comorbidity interfering with therapy compliance and follow-up compliance
• Pregnancy
• Patients not willing or who are not able to comply with contraceptive measures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Prof.dr. J.C. Kluin-Nelemans

Prof.dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

J.C. Kluin-Nelemans, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, Provincie Groningen, Netherlands

Countries

Netherlands

References

van Anrooij B, Oude Elberink JNG, Span LFR, de Monchy JGR, Rosati S, Mulder AB, Kluin-Nelemans JC. Midostaurin in patients with indolent systemic mastocytosis: An open-label phase 2 trial. J Allergy Clin Immunol. 2018 Sep;142(3):1006-1008.e7. doi: 10.1016/j.jaci.2018.06.003. Epub 2018 Jun 8. No abstract available.

Reference Type: DERIVED

PMID: 29890238 (View on PubMed)

Other Identifiers

UMCG41973

Identifier Type: -

Identifier Source: org_study_id