Midostaurin in Indolent Systemic Mastocytosis

January 15, 2015 updated by: Prof.dr. J.C. Kluin-Nelemans, University Medical Center Groningen

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.

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9700RB
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Midostaurin
Treatment with Midostaurin, twice daily 100 mg orally for 6 months continuously.
Drug: Midostaurin,
Midostaurin, twice daily 100 mg orally, continuously for 6 months
Other Names:
  • PKC412

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptom Scoring
Time Frame: 12 weeks
Percent change in the total score ("Sumscore") of all symptoms assessed by the Mastocytosis Symptom Assessment Form (MSAF) after 12 weeks.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Persistence of improvements
Time Frame: 6 months
persistence of improvement symptom score at 6 months.
6 months
Mast cell burden
Time Frame: 6 months
Percent change in the mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase levels) after 6 months.
6 months
Adverse events
Time Frame: 6 months
Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: J.C. Kluin-Nelemans, MD, PhD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Anticipated)

March 1, 2015

Study Completion (Anticipated)

May 1, 2015

Study Registration Dates

First Submitted

August 7, 2013

First Submitted That Met QC Criteria

August 7, 2013

First Posted (Estimate)

August 9, 2013

Study Record Updates

Last Update Posted (Estimate)

January 19, 2015

Last Update Submitted That Met QC Criteria

January 15, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCG41973

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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