Study of Mast Cell Precursors - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00001756

Purpose

This study will investigate mast cell precursors that circulate in the blood. In a group of diseases collectively known as mastocytosis, mast cells accumulate in abnormal amounts in the skin, lymphoid tissues, bone marrow, liver and spleen. Some forms of mastocytosis have a generally good prognosis; for others, the prognosis is poorer. There is no known cure for any form of the disease. A better understanding of mast cells and how they respond to certain substances may provide insights that will lead to effective treatments for mastocytosis.

Patients with systemic mastocytosis and normal healthy volunteers between the ages of 20 and 60 may be eligible for this 8-day study. Participants will undergo the following procedures:

Day 1 - Medical history, physical examination, and blood tests to assess general health status
Days 2 through 6 - Daily injections under the skin of G-CSF-a hormone that stimulates white blood cell production
Day 7 - Leukapheresis-a procedure for collecting large numbers of white blood cells. In leukapheresis, blood is drawn through a needle placed in an arm and channeled into a cell separator machine. The white cells are collected and the rest of the blood is returned to the body through a needle in the other arm. The procedure takes up to 3 hours.
Days 7 and 8 - Blood draw (about 1 teaspoon) to monitor white blood cell counts.

Condition
Mastocytosis

Study Type:	Observational
Official Title:	The Characterization of CD34+ Derived Mast Cell Precursors Mobilized by Administration of Granulocyte Colony Stimulating Factor

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	200
Study Start Date:	November 1997
Estimated Study Completion Date:	August 2000
Estimated Primary Completion Date:	August 2000 (Final data collection date for primary outcome measure)

Detailed Description:

The purpose of this protocol is to obtain large numbers of CD34+ cells from the peripheral blood of patients with systemic mastocytosis and normal volunteers by leukapheresis for culture and characterization of mast cell progenitor cells and their response to various cytokines and anti-mitotic agents. Granulocyte colony stimulating factor (G-CSF) will be administered to normal volunteers at doses of 10 microg/kg/day as a single subcutaneous dose daily for 5 days. Normal volunteers and mastocytosis patients will be adults of both sexes from 18 to 60 years of age. Normal volunteers and patients will undergo a single leukapheresis at day 7. A small number of normal volunteers and all mastocytosis patients will undergo leukapheresis without G-CSF mobilization. This is not a therapeutic protocol and does not involve reinfusion of any manipulated cells, viruses or DNA constructs back into human subjects.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

INCLUSION CRITERIA:

Normal Volunteers - ages 18-60:

Healthy without active infection or history of recurrent infections.

Normal renal function (creatinine less than or equal to 1.5 mg/dl; less than or equal to 1+ proteinuria); normal hepatic function (bilirubin less than or equal to 1.5 mg/dl); normal hematologic function (WBC greater than or equal to 3000/mm(3); granulocytes greater than or equal to 1500/mm(3); platelets greater than or equal to 175,000; hemoglobin greater than or equal to 12.5).

Normal female volunteers of childbearing potential may be entered if using contraception, and with a negative urine pregnancy test determined the day before beginning G-CSF administration.

Patients - ages 18-60:

Systemic mastocytosis patients must have mast cell hyperplasia compatible with a diagnosis of systemic mastocytosis; and be without active infection or history of recurrent infections.

Preserved renal function (creatinine less than or equal to 2mg/dl; less than or equal to 2+ proteinuria); preserved hepatic function (bilirubin less than or equal to 1.5 mg/dl); preserved hematologic function (WBC greater than or equal to 3000/mm(3), granulocytes greater than or equal to 1500/mm(3); platelets greater than or equal to 175,000; hemoglobin greater than or equal to 12.5).

Normal female volunteers of childbearing potential may be entered if using effective contraception, and with a negative urine pregnancy test determined the day before beginning G-CSF administration.

EXCLUSION CRITERIA:

NORMAL VOLUNTEERS:

Active bacterial, fungal or viral infections.

HIV+, HCV+.

Pregnancy or lactation.

History of autoimmune disease such as rheumatoid arthritis, vasculitis, pyoderma gangrenosum or similar disorder.

Use of any investigative drugs.

History of splenic trauma.

Any condition which in the judgment of the PI might significantly increase the risks of mobilization or aphereses.

SYSTEMIC MASTOCYTOSIS PATIENTS:

Active bacterial, fungal or viral infections.

HIV+, HCV+.

Patients taking any other growth factors, cytokines or investigative drugs.

Patients hemodynamically unstable (blood pressure systolic of lower than 105 or diastolic lower than 65).

Pregnancy or lactation.

History of autoimmune disease such as rheumatoid arthritis, vasculitis, pyoderma gangrenosum or similar disorder.

Any condition which in the judgment of the PI might significantly increase the risks of mobilization or aphereses.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001756

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Nagata H, Worobec AS, Oh CK, Chowdhury BA, Tannenbaum S, Suzuki Y, Metcalfe DD. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10560-4.

Kirshenbaum AS, Kessler SW, Goff JP, Metcalfe DD. Demonstration of the origin of human mast cells from CD34+ bone marrow progenitor cells. J Immunol. 1991 Mar 1;146(5):1410-5.

Rottem M, Okada T, Goff JP, Metcalfe DD. Mast cells cultured from the peripheral blood of normal donors and patients with mastocytosis originate from a CD34+/Fc epsilon RI- cell population. Blood. 1994 Oct 15;84(8):2489-96.

Study ID Numbers:	980027, 98-I-0027
Study First Received:	November 3, 1999
Last Updated:	June 9, 2009
ClinicalTrials.gov Identifier:	NCT00001756 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Leukapheresis
Mastocytosis
G-CSF
Mast Cells

Progenitors
Normal Volunteer
Systemic Mastocytosis

Study placed in the following topic categories:

Neoplasms, Connective and Soft Tissue
Mast Cell Disease
Skin Diseases
Mastocytosis, Systemic

Mastocytoma
Mastocytosis
Systemic Mastocytosis

Additional relevant MeSH terms:

Neoplasms, Connective and Soft Tissue
Neoplasms
Neoplasms by Histologic Type
Skin Diseases

Mastocytoma
Mastocytosis
Neoplasms, Connective Tissue

ClinicalTrials.gov processed this record on July 02, 2009