Assess the Feasibility and Safety of Granulocyte Colony Stimulating Factor (GCSF) Mobilization of CD34+ Hematopoietic Progenitor Cells in Patients With Betathalassemia Major

Beta Thalassemia Major Clinical Trial

Official title:

A Pilot Trial to Assess the Feasibility and Safety of GCSF Mobilization of CD34+ Hematopoietic Progenitor Cells in Patients With Betathalassemia Major

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00658385
• Other study ID #: 08-030
• Status: Completed
• Phase: N/A
• First received: April 10, 2008
• Last updated: February 11, 2011
• Start date: April 2008
• Est. completion date: February 2011

Study information

• Verified date: February 2011
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Betathalassemia major is a disease of the blood and bone marrow. You were born with it and it has made you unable to make normal hemoglobin and red cells. You have been receiving red blood cell transfusions all your life. These transfusions do not cure your disease. The problem with transfusions is that they contain a lot of iron. With time iron builds up in your body and will eventually hurt some of your organs . Because of this buildup of iron , you are taking medicine that helps your body get rid of the extra iron.

Today, the only other treatment is bone marrow or stem cell transplant. It can only be done when a matched donor is available. This is most often a brother, sister, or parent. Bone marrow transplant may cure betathalassemia major. If you have a transplant and it is successful, you will no longer have the disease. Without a matched sibling or parent, the standard treatment is to keep having transfusions.

In the near future, we will be testing a new treatment for making normal hemoglobin and normal red blood cells. We have recreated the healthy hemoglobin gene in a test tube. We are able to use it and put it back into cells. This is called gene therapy. We have been able to put this gene into the stem cells of mice with thalassemia. These mice were cured. We now plan to take that gene and put it into stem cells from people who have betathalassemia major. We will then inject those stem cells back into that person's blood.

In general, we can obtain more stem cells from the blood of a person than from the bone marrow . In order to do so, we must give that person a blood growth factor. The growth factor stimulates the bone marrow to make more stem cells. That growth factor is called granulocyte colony stimulating factor (GCSF), or Filgrastim.

The purpose of this trial is to find out if the drug GCSF has any side effects on you, and if you will make more stem cells in response to it. This trial is not a gene therapy trial. This trial will not help your thalassemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must be 18 years or older

• Subjects may be of either gender or of any ethnic background

• Subjects must have a confirmed diagnosis of ßthalassemia major and have been enrolled in a hypertransfusion program with a confirmed annual transfusion of = or = to 100 mL/kg/yr AND = or = to 8 Transfusions of blood per year over a minimum of two years.

• Patients must be off hydroxyurea (HU) or erythropoietin (EPO) treatment for at least three months prior to entry onto the study

• Subjects must have a performance score of Karnofsky > or = to 70 of the time of entry into the study.

• Subjects must have a normal EKG and a normal chest xray

• Each patient must be willing to participate as a research subject and must sign an informed consent form.

• Subjects must be splenectomized or have no palpable spleen

• Negative pregnancy test, if female

Exclusion Criteria:

• Active infections including Hepatitis B and C, HTLV 1 and 2, West Nile Virus, and HIV 1

• Female patient pregnant or breast feeding

• Patients with uncontrolled seizure disorders

• Allergy to GCSF or bacterial E. coli products

• History of sickle cell disease or sickle trait

• History of thrombosis or known thrombophilia

Study Design

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

Related Conditions & MeSH terms

• Beta Thalassemia Major
• Beta-Thalassemia
• Congenital Anemias
• Thalassemia

Intervention

Genetic:
• GCSF, Central venous line placement, Stem cell Collection (leukapheresis)
Daily injections under the skin of a GCSF. This is done for 5 to 6 days. On days 1, 3,5, and if need on day 6. To collect stem cells, we need good access to this blood. If the patient has good veins, we do this by placing an IV on each one of their arms. The peripheral blood stem cell collection is usually an outpatient procedure and takes about 3 to 4 hours. You will have blood work and a physical exam on days one, three, and five while you are getting GCSF. These will be done again 24 hours after your stem cells are collected.

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To investigate the feasibility and safety of peripheral blood hematopoietic progenitor cell (HPC) mobilization with GCSF in patients with ßthalassemia major and to determine the yield of CD34+ HPCs mobilized.		conclusion of study	Yes
Secondary	To determine whether the collected HPCs are amenable to transduction with a lentiviral vector encoding the normal ßglobin gene.		conclusion of study	No

External Links

•   Memorial Sloan-Kettering Cancer Center