Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis

Sponsor

Hospital Virgen de la Salud (Other)

Overall Status

Unknown status

CT.gov ID

NCT01602939

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Systemic Mastocytosis	Drug: Cladribine and pegylated interpheron alpha-2a	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2012

Anticipated Primary Completion Date :

Feb 1, 2017

Anticipated Study Completion Date :

Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2CDA+IFN	Drug: Cladribine 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.

Arm

Intervention/Treatment

Experimental: 2CDA+IFN

Drug: Cladribine 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 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 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.