Midostaurin in Indolent Systemic Mastocytosis

Indolent Systemic Mastocytosis Clinical Trial

Official title:

Phase II Single Arm Open Pilot Study to Demonstrate the Efficacy of Midostaurin in Symptom Improvement and Decrease of Mast Cell Burden in Patients With Indolent or Smoldering Systemic Mastocytosis.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01920204
• Other study ID #: UMCG41973
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 7, 2013
• Last updated: January 15, 2015
• Start date: August 2013
• Est. completion date: May 2015

Study information

• Verified date: January 2015
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: May 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Indolent Systemic Mastocytosis
• Mastocytosis

Intervention

Drug:
• Midostaurin,
Midostaurin, twice daily 100 mg orally, continuously for 6 months

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Symptom Scoring	Percent change in the total score ("Sumscore") of all symptoms assessed by the Mastocytosis Symptom Assessment Form (MSAF) after 12 weeks.	12 weeks	No
Secondary	Persistence of improvements	persistence of improvement symptom score at 6 months.	6 months	No
Secondary	Mast cell burden	Percent change in the mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase levels) after 6 months.	6 months	No
Secondary	Adverse events	Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.	6 months	Yes