Systemic Mastocytosis
Conditions
Keywords
Mast cell, Mastocytosis, Mast cell disease
Brief summary
The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Cladribine plus Pegylated Interpheron alpha-2a therapy in patients with advanced systemic mastocytosis carrying D816V or other exon 17 KIT mutations.
Interventions
DRUGCladribine and pegylated interpheron alpha-2a
Cladribine (0.07 mg/Kg/day) s.c for 5 consecutive days each month for a total of 6 months.Cladribine daily doses could be increased up to 0.14 mg/Kg in the fourth, fifth and sixth cycles of therapy if no objetive response is achieved after the third cycle. Pegylated Interpheron alpha-2a (1 mcgr/Kg) s.c weekly for a total of 6 months.
Sponsors
Hospital Virgen de la Salud
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
* Age older than 18 years. * Diagnosis of advanced systemic mastocytosis (aggressive systemic mastocytosis or proggressing systemic mastocytosis) with D816V or other exon 17 KIT mutations. * ECOG ≤ 3. * Signed informed consent.
Exclusion criteria
* Impaired liver function (total bilirubin ≥ 2.0 mg/dl, AST or ALT \> 3 x upper limit of normal)not related to mastocytosis. * Impaired renal function (≥ 2.0 mg/dL)not related to mastocytosis. * Grade III-IV cytopenias not related to mastocytosis. Severe cardiopathy (grade III/IV of NYHA, or left ventricular ejection fraction \< 50%). * Pregnancy or breastfeeding. * Female patients who do not use contraceptive methods.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect of therapy on bone marrow mast cell infiltration. | 6 months | Evaluation of bone marrow response will be assessed by immunohistochemestry, citology, flow cytometry and molecular analyses of bone marrow samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect of therapy on mast cell-mediator release symptoms: pruritus, flushing, gastrointestinal symptoms or anaphylaxis). | 6 months | Specific questionnaires regarding mast cell-mediator release symptoms will be filled monthly by each patient until the end of therapy. |
| To determine de safety of combined therapy with low doses of cladribine plus pegylated interpheron alpha-2a. | 6 months | Potentially drugs-related adverse events will be recorded in each case following accepted criteria (NIH CTCAE). |
| To determine the effect of therapy on serum tryptase levels and other altered peripheral blood parameters due to mastocytosis. | 6 months | Serum tryptase and any other mastocytosis-related altered biochemical parameter at diagnosis will be measured monthly until the end of therapy. |
| To evaluate the effect of therapy on mastocytosis-related organomegalies. | 6 months | Evaluation of organomegalies response will be assessed by abdominal ultrasound and/or computerized tomography. |
| To evaluate the effect of therapy on mastocytosis-related bone alterations. | 6 months | Evaluation of bone response will be assessed by X-ray survey and/or computerized tomography. |
| To evaluate the effect of therapy on mastocytosis skin lesions. | 6 moths | Evaluation of cutaneous response will be assessed by macroscopic inspection including photographs and by skin immunohistochemestry. |
Countries
Spain
Contacts
Primary ContactLuis Escribano, MD, PhD
Backup ContactIván Alvarez-Twose, MD
Outcome results
None listed