Midostaurin in Indolent Systemic Mastocytosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University Medical Centre Groningen
Sponsor:
Information provided by (Responsible Party):
Prof.dr. J.C. Kluin-Nelemans, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01920204
First received: August 7, 2013
Last updated: October 11, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Indolent Systemic Mastocytosis
Drug: Midostaurin,
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Symptom Scoring [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    persistence of improvement symptom score at 6 months.

  • Mast cell burden [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Percent change in the mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase levels) after 6 months.

  • Adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy.


Estimated Enrollment: 20
Study Start Date: August 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: PKC412

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01920204

Contacts
Contact: J.C. Kluin-Nelemans, MD, PhD 0031503612354 hematologiestudie@umcg.nl

Locations
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands, 9700RB
Sponsors and Collaborators
University Medical Centre Groningen
Investigators
Principal Investigator: J.C. Kluin-Nelemans, MD, PhD University Medical Centre Groningen
  More Information

No publications provided

Responsible Party: Prof.dr. J.C. Kluin-Nelemans, Prof.dr., University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01920204     History of Changes
Other Study ID Numbers: UMCG41973
Study First Received: August 7, 2013
Last Updated: October 11, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:
Mastocytosis
ISM
SSM

Additional relevant MeSH terms:
Urticaria Pigmentosa
Mastocytosis
Mastocytosis, Systemic
Mastocytosis, Cutaneous
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Pigmentation Disorders
Skin Diseases
4'-N-benzoylstaurosporine
Staurosporine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014