Indolent Systemic Mastocytosis
Conditions
Keywords
Mastocytosis, ISM, SSM
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.
Interventions
DRUGMidostaurin,
Midostaurin, twice daily 100 mg orally, continuously for 6 months
Sponsors
University Medical Center Groningen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Scoring | 12 weeks | Percent change in the total score (Sumscore) of all symptoms assessed by the Mastocytosis Symptom Assessment Form (MSAF) after 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistence of improvements | 6 months | persistence of improvement symptom score at 6 months. |
| Mast cell burden | 6 months | Percent change in the mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase levels) after 6 months. |
| Adverse events | 6 months | Number and grading of Common Terminology Criteria adverse events during the 6 months of therapy. |
Countries
Netherlands
Outcome results
None listed