Evaluating the Safety of G-CSF Mobilization in Individuals With Beta Thalassemia Major

NCT00336362 | Completed DMC

• 4 other identifiers: 4642U01HL066947IRB no. 27527EudraCT no. 2005-000315-10
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Beta thalassemia major is a serious genetic disease of the blood. Treatments are limited, and although a bone marrow transplant from a compatible donor can be curative, only a limited percentage of individuals with this disease have a matched donor available. A long-term goal of study researchers is to develop a gene transfer process as a method of curing beta thalassemia major. Gene transfer involves obtaining blood stem cells from an individual, adding a normal globin gene to the stem cells, and putting the cells back into the individual. Before gene transfer methods can be attempted in individuals with beta thalassemia major, a safe method of obtaining blood stem cells needs to be developed. The purpose of this study is to investigate the safety and feasibility of collecting peripheral blood stem cells (PBSC) from individuals with beta thalassemia major. Research participants will be given G-CSF (filgrastim) for several days to increase the number of stem cells in the blood, a process called "mobilization." After mobilization, participants will undergo a procedure called apheresis to remove the white blood cells. Researchers in the laboratory will purify the stem cells from the mixture and test methods of putting a normal globin gene into the stem cells. Half of the participants will receive hydroxyurea (HU) prior to G-CSF mobilization. HU is used in splenectomized patients to attempt to reduce the risk of clotting during mobilization. In non-splenectomized patients, HU is given in an attempt to decrease the size of the spleen.

Conditions

Beta-Thalassemia

Keywords

Beta Thalassemia Major; Hematopoietic Stem Cell Mobilization; Gene Transfer Techniques

Outcome Measures

Primary Outcomes (1)

• Safety of PBSC mobilization with G-CSF with or without hydroxyurea pretreatment in adults with beta thalassemia major

  Measured at Month 2

Secondary Outcomes (2)

• Number of CD34+ stem/progenitor cells that are mobilized

  Measured at Month 2

• Ability of the obtained stem cells to be transduced with a recombinant lentivirus vector for beta-globin and engraft immunodeficient mice

  Measured at Year 1

Study Arms (2)

1

ACTIVE COMPARATOR

Participants will receive hydroxyurea pretreatment.

Drug: Hydroxyurea

2

NO INTERVENTION

Participants will not receive hydroxyurea pretreatment.

Interventions

Hydroxyurea DRUG

Hydroxyurea: Subjects will be treated for one month with hydroxyurea at a starting dose of 10 mg/kg orally (closest approximation to 500 mg capsule, alternate day dosing, e.g. 500 alternating with 1000 to achieve 750 mg average daily dose), once daily, with a gradual dose escalation up to 20 mg/kg (in non-splenectomized patients) and up to 25 mg/kg (in splenectomized patients). G-CSF: G-CSF will be administered subcutaneously. In general, G-CSF will be administered at 10μg/kg/day (5μg/kg on a twice a day schedule) for at least 4-5 days before leukapheresis and for 1-2 additional days during collections. For the splenectomized patients who are not receiving HU pretreatment, and for the splenectomized patients who receive HU pretreatment who have greater than or equal to 12,000 WBCs before G-CSF, G-CSF will start at a lower dose (for example, 1.5 or 2.5 µg/kg); the next doses will be adjusted by the Principal Investigator based on the observed degree of leukocytosis.

Also known as: hydrea

1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• β-thalassemia major
• Karnofsky performance status greater than or equal to 80%
• Splenectomized patients or patients with spleen volume less than 800 cm\^3 (V=0.523 x length x thickness x width)
• Compliant with regular transfusions and regular chelation
• Liver iron by magnetic resonance imaging (MRI) less than 280 μmol/gr or greater than or equal to 1.7 msec by T2\*MRI
• Heart iron by MRI greater than 2.8 (SI/SD)or greater than or equal to 9 msec by T2\*MRI
• Hepatitis B or C virus load negative by polymerase chain reaction (PCR)
• Left ventricular ejection fraction (LVEF) greater than 45% by echocardiogram or multiple gated acquisition scan (MUGA)
• Adequate respiratory function with diffusing capacity of the lung for carbon monoxide (DLCO) greater than 50%
• Negative pregnancy test, if female
• Ability to give informed consent and willingness to meet all the expected requirements of the protocol for the duration of the study

You may not qualify if:

• History of thrombosis or known thrombophilia
• Symptomatic viral, bacterial, or fungal infection within 6 weeks of eligibility evaluation
• Pregnant or breastfeeding
• HIV positivity
• History of cancer, other than local skin cancer
• Other systematic disease
• Splenectomized patients with platelet count greater than 900,000
• Additional risk factors for thrombosis, including Factor V Leiden; antiphospholipid antibodies; and less than 50% of the lowest normal value for the following procoagulants: antithrombin 3, protein C, or protein S

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• George Papanicolaou Hospital: collaborator

Study Sites (1)

George Papanicolaou Hospital

Thessaloniki, Greece

Location

MeSH Terms

Conditions

beta-Thalassemia

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• George Stamatoyannopoulos, MD, DrSci

  University of Washington

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2006
• First Posted: June 13, 2006
• Study Start: July 1, 2006
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: December 20, 2012

Record last verified: 2012-12

Locations

GR (1)