Study of Mast Cell Precursors

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT00001756

Collaborator

(none)

300

Enrollment

Location

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Mastocytosis Healthy Volunteer

Detailed Description

The purpose of this protocol is to obtain large numbers of CD34+ cells from the peripheral blood of healthy volunteers and patients with systemic mastocytosis or other related allergic, hematological, and immunological conditions by leukapheresis for culture and characterization of mast cell progenitor cells and their response to various cytokines and anti-mitotic agents. Healthy volunteers and patients will be adults of both sexes from 18 to 70 years of age. Granulocyte colony stimulating factor (G-CSF) will be administered to healthy volunteers at dose of 10 mcg/kg/day as a subcutaneous dose daily for 5 days not to exceed 960mcg. Patients will receive Plerixafor at a dose of 0.24 mg/kg as a single subcutaneous dose not to exceed 24mg the night before leukapheresis as a mobilizing agent for CD34+ cells. In identified patients where leukapheresis yield is considered adequate without stimulation by the principal investigator, leukapheresis may proceed without stimulation. Healthy volunteers will undergo a single leukapheresis at day 7, and patients will undergo a single leukapheresis at day 3 or 4. This is not a therapeutic protocol and does not involve reinfusion of any manipulated cells, viruses or DNA constructs back into human subjects.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

The Characterization of CD34+ Derived Mast Cell Precursors

Actual Study Start Date :

Dec 3, 1997

Arms and Interventions

Arm	Intervention/Treatment
Healthy Volunteers Healthy Volunteers
Patients Patients have mast cell hyperplasia compatible with a diagnosis of systemic mastocytosis (applicable to systemic mastocytosis patients only) or other allergic, hematologic, orimmunologic condition.

Outcome Measures

Primary Outcome Measures

Use of G-CSF administration healthy volunteers to mobilize and enhance CD34+ hematopoietic progenitor cell numbers into the peripheral blood in order to culture and characterize human mast cells, study and characterize CD34+ -derived human ma... [12/31/2029]
Use of G-CSF administration healthy volunteers to mobilize and enhance CD34+ hematopoietic progenitor cell numbers into the peripheral blood in order to culture and characterize human mast cells, study and characterize CD34+ -derived human mast cells.
Collection of CD34+ cells with or without use of Plerixafor administration in patients with systemic mastocytosis and other related allergic, hematological and immunological conditions to mobilize and enhance CD34+ cells into the peripheral b... [12/31/2029]
Collection of CD34+ cells with or without use of Plerixafor administration in patients with systemic mastocytosis and other related allergic, hematological and immunological conditions to mobilize and enhance CD34+ cells into the peripheral blood to culture and learn how mast cells contribute to these disease states.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

SUBJECT INCLUSION CRITERIA:

Healthy Volunteers must:

Be 18-70 years of age
Be healthy
Have adequate peripheral venous access
Have normal renal function (creatinine less than or equal to 1.5mg/dL; less than or equal to 1 plus proteinuria)
Have normal hepatic function (bilirubin less than or equal to 1.5 mg/dL)
Have 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 g/dL)

Patients must:

Be 18-70 years of age
Have mast cell hyperplasia compatible with a diagnosis of systemic mastocytosis (applicable to systemic mastocytosis patients only) or other allergic, hematologic, or immunologic condition
Have adequate peripheral venous access or be willing to have a central line placed.
First be admitted as inpatients under an existing NIH protocol
Have preserved renal function (creatinine less than or equal to 2 mg/dL; less than or equal to 2 plus proteinuria)
Have preserved hepatic function (bilirubin less than or equal to 1.5 mg/dL)
Have 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 g/dL)

All female subjects of childbearing potential:

May be enrolled if using effective contraception
Have a negative serum or urine pregnancy test determined within 72 hours before beginning Plerixafor or G-CSF administration

SUBJECT EXCLUSION CRITERIA:

All subjects must not meet any of the following criteria:

Healthy Volunteers and patients must not:

Have active bacterial, fungal or viral infections
Have viral screens positive for HIV or hepatitis B or C
Be pregnant or lactating
Have a history of autoimmune disease such as rheumatoid arthritis, vasculitis, pyoderma gangrenosum or similar disorder
Have any condition, which in the judgment of the investigator, might place the subject at undue risk

Healthy Volunteers with any of the following will be excluded:

Splenomegaly, pulmonary fibrosis and other related conditions
Use of any investigative drugs within the past 12 months
Have a significant coagulation disorder

Systemic Mastocytosis and Mast Cell Related Condition Patients with any of the following will be excluded:

Patients taking any other growth factors, cytokines or investigative drugs
Patients who are hemodynamically unstable (blood pressure systolic of lower than 105 or diastolic lower than 65)