Primary: To study the efficacy and tolerability of Midostaurin in patients with indolent or smoldering systemic mastocytosis on mediator symptom reduction.Secondary: 1) To study whether Midostaurin can reduce mast cell infiltration and 2) to assess…
ID
Source
Brief title
Condition
- Haematopoietic neoplasms (excl leukaemias and lymphomas)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percent change in the Sumscore of all symptoms assessed by the Mastocytosis
Symptom Assessment Form (MSAF) after 12 weeks.
Secondary outcome
Persistence of improvement symptom score at 6 months. Percent change in the
mast cell burden (bone marrow infiltrate, skin infiltrate, serum tryptase
levels) after 6 months. Number and grading of CTC adverse events during the 6
months of therapy.
Background summary
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. Since 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 a rare subset of systemic mastocytosis,
the aggressive form.
Study objective
Primary: To study the efficacy and tolerability of Midostaurin in patients with
indolent or smoldering systemic mastocytosis on mediator symptom reduction.
Secondary: 1) To study whether Midostaurin can reduce mast cell infiltration
and 2) to assess its safety in this group of patients.
Study design
Single arm, open label pilot phase II study.
Intervention
treatment with Midostaurin, twice daily 100 mg orally for 6 months
continuously.
Study burden and risks
Risks and burden: Patients will take an experimental drug with thus far as
frequent adverse event nausea and vomiting (<3% CTC grade 3-4) that can be well
controlled by antiemetic drugs. Other adverse events mentioned are all at a CTC
grade 3-4 frequency of less than 2%. Patients have to fill in a 2 page symptoms
score weekly. They will undergo an abdominal ultrasound and bone marrow
examination twice (pre and post treatment), unless the pre-sample is a recent
one. They will visit the UMCG 9 times including the pre-visit. At each visit
blood tests will be taken (chemistry control, hemogram, tryptase levels).
Benefit: this is the first time that a potentially effective mast-cell
eradicative therapy with very promising results regarding symptom improvement
is offered to patients with symptomatic systemic mastocytosis for whom
guidelines thus far do not prescribe such eradicative therapy. If successful
with a managable adverse events pattern, a large majority of patients with this
subset of mastocytosis (the predominant form) will benefit.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
* Patients with ISM or 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 form15) with at least
o a pre-study score of 4 or more on 3 non-related items,
o or a pre-study score of 5 or more on 2 non-related items.
o 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) if applicable, e.g. 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-004868-22-NL |
| CCMO | NL41973.042.12 |