Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis

Study Overview
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Brief Summary
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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.

Official Title
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Subcutaneous Cladribine Plus Pegylated Interpheron Alfa-2a in Advanced Systemic Mastocytosis With D816V and Other Exon 17 KIT Mutations.

Conditions
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Systemic Mastocytosis

Intervention / Treatment
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* Drug: Cladribine and pegylated interpheron alpha-2a


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2CDA+IFN<br> | Drug: Cladribine and pegylated interpheron alpha-2a<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of therapy on bone marrow mast cell infiltration. | Evaluation of bone marrow response will be assessed by immunohistochemestry, citology, flow cytometry and molecular analyses of bone marrow samples. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of therapy on serum tryptase levels and other altered peripheral blood parameters due to mastocytosis. | Serum tryptase and any other mastocytosis-related altered biochemical parameter at diagnosis will be measured monthly until the end of therapy. | 6 months | 
| To evaluate the effect of therapy on mast cell-mediator release symptoms: pruritus, flushing, gastrointestinal symptoms or anaphylaxis). | Specific questionnaires regarding mast cell-mediator release symptoms will be filled monthly by each patient until the end of therapy. | 6 months | 
| To determine de safety of combined therapy with low doses of cladribine plus pegylated interpheron alpha-2a. | Potentially drugs-related adverse events will be recorded in each case following accepted criteria (NIH CTCAE). | 6 months | 
| To evaluate the effect of therapy on mastocytosis skin lesions. | Evaluation of cutaneous response will be assessed by macroscopic inspection including photographs and by skin immunohistochemestry. | 6 moths | 
| To evaluate the effect of therapy on mastocytosis-related organomegalies. | Evaluation of organomegalies response will be assessed by abdominal ultrasound and/or computerized tomography. | 6 months | 
| To evaluate the effect of therapy on mastocytosis-related bone alterations. | Evaluation of bone response will be assessed by X-ray survey and/or computerized tomography. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mast cell, Mastocytosis, Mast cell disease