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Midostaurin in Indolent Systemic Mastocytosis

Primary Purpose

Indolent Systemic Mastocytosis

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Midostaurin,
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Indolent Systemic Mastocytosis focused on measuring Mastocytosis, ISM, SSM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Medical Center Groningen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Midostaurin

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 7, 2013
Last Updated
January 15, 2015
Sponsor
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT01920204
Brief Title
Midostaurin in Indolent Systemic Mastocytosis
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Unknown status
Study Start Date
August 2013 (undefined)
Primary Completion Date
March 2015 (Anticipated)
Study Completion Date
May 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indolent Systemic Mastocytosis
Keywords
Mastocytosis, ISM, SSM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Midostaurin
Arm Type
Experimental
Arm Description
Treatment with Midostaurin, twice daily 100 mg orally for 6 months continuously.
Intervention Type
Drug
Intervention Name(s)
Midostaurin,
Other Intervention Name(s)
PKC412
Intervention Description
Midostaurin, twice daily 100 mg orally, continuously for 6 months
Primary Outcome Measure Information:
Title
Symptom Scoring
Description
Percent change in the total score ("Sumscore") of all symptoms assessed by the Mastocytosis Symptom Assessment Form (MSAF) after 12 weeks.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Persistence of improvements
Description
persistence of improvement symptom score at 6 months.
Time Frame
6 months
Title
Mast cell burden
Description
Percent change in the mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase levels) after 6 months.
Time Frame
6 months
Title
Adverse events
Description
Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J.C. Kluin-Nelemans, MD, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700RB
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
29890238
Citation
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.
Results Reference
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Midostaurin in Indolent Systemic Mastocytosis

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