Cladribine Plus Pegylated Interpheron Alfa-2a in Systemic Mastocytosis

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

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.

Study Overview

• Status: Unknown
• Conditions: Systemic Mastocytosis
• Intervention / Treatment: Drug: Cladribine and pegylated interpheron alpha-2a

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Luis Escribano, MD, PhD; Phone Number: +34925269335; Email: lescribanom@sescam.jccm.es
• Study Contact Backup: Name: Iván Alvarez-Twose, MD; Phone Number: +34925269336; Email: ivana@sescam.jccm.es

Study Locations

• Spain
  • Toledo, Spain, 45071
    • Recruiting
    • Instituto de Estudios de Mastocitosis de Castilla La Mancha; Hospital Virgen del Valle
    • Contact: Luis Escribano, MD, PhD; Phone Number: +34925269335; Email: lescribanom@sescam.jccm.es
    • Contact: Iván Alvarez-Twose, MD; Phone Number: +34925269336; Email: ivana@sescam.jccm.es
    • Principal Investigator: Luis Escribano, MD, PhD
    • Sub-Investigator: Iván Alvarez-Twose, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Virgen de la Salud
• Investigators: Principal Investigator: Luis Escribano, MD, PhD, Instituto de Estudios de Mastocitosis de Castilla La Mancha

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Anticipated): February 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: May 16, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 21, 2012

Study Record Updates

• Last Update Posted (Estimate): August 29, 2016
• Last Update Submitted That Met QC Criteria: August 26, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Mast cell; Mastocytosis; Mast cell disease
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Hypersensitivity; Neoplasms, Connective Tissue; Immune Complex Diseases; Mastocytosis; Mastocytosis, Systemic; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cladribine
• Other Study ID Numbers: EC11-187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No