Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis

Systemic Mastocytosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01602939
• Other study ID #: EC11-187
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: May 16, 2012
• Last updated: August 26, 2016
• Start date: May 2012
• Est. completion date: June 2017

Study information

• Verified date: August 2016
• Source: Hospital Virgen de la Salud
• Contact: Luis Escribano, MD, PhD
• Phone: +34925269335
• Email: lescribanom[@]sescam.jccm.es
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mastocytosis
• Systemic Mastocytosis

Intervention

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.

Locations

Country	Name	City	State
Spain	Instituto de Estudios de Mastocitosis de Castilla La Mancha; Hospital Virgen del Valle	Toledo

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Virgen de la Salud

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No