Beta-ThalassemiaNCT00336362
Evaluating the Safety of G-CSF Mobilization in Individuals With Beta Thalassemia Major
A study testing Hydroxyurea in people with Beta-Thalassemia, run by University of Washington at 1 site in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Beta-Thalassemia
- What is being tested?
- Hydroxyurea
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteGreece
- Study dates
- Jul 2006to Aug 2010
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study to Assess the Safety and Efficacy of G-CSF Mobilization With and Without Hydroxyurea Pretreatment in Adults With Beta Thalassemia Major
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.
Read the detailed description
Primary Objective: To determine the safety of PBSC mobilization with G-CSF, with or without HU pretreatment in adults with beta thalassemia major.
Secondary Objective: To determine the number of CD34+ stem/progenitor cells that are mobilized under these conditions, as well as the ability of these cells to be transduced with a recombinant lentivirus vector for beta-globin and engraft immunodeficient mice.
Study Design: The ability of G-CSF to safely and effectively mobilize PBSC in adults with beta thalassemia major will be assessed in 12 splenectomized and 12 non-splenectomized patients. Of the 12 splenectomized patients, 6 will be treated with HU and G-CSF, and 6 will be treated only with G-CSF. Likewise, of the 12 non-splenectomized patients, 6 will be treated with HU and G-CSF, and 6 will be treated only with G-CSF. G-CSF mobilized participants will undergo leukapheresis on 2 consecutive days, with a target yield of 2 million CD34+ cells per kg of body weight. Safety will be assessed by monitoring for study-related toxicity. Efficacy will be assessed by measuring the total number of CD34+ cells, the ability of these cells to be transduced with a recombinant lentivirus vector for beta-globin, and the ability of these cells to engraft immunodeficient mice.
Population: Adults with beta thalassemia major.
Sample size: A total of 24 subjects will be enrolled: 12 splenectomized participants and 12 non-splenectomized participants.
End Points: This is a pilot study and no specific hypotheses are being tested. However, the study will allow for qualitative comparisons if outcomes between the various arms are markedly different. For example, the study will provide qualitative data on the safety and feasibility of utilizing HU and G-CSF to mobilize stem cells in individuals with beta thalassemia major. The study will be completed upon full enrollment, or when stopping criteria are met within specific study arms.
- Conditions
- Beta-Thalassemia
- Being tested
- Hydroxyurea
- Keywords
- Beta Thalassemia Major, Hematopoietic Stem Cell Mobilization, Gene Transfer Techniques
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Also called hydrea
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Participants will receive hydroxyurea pretreatment. Receives: Drug: Hydroxyurea |
| 2 | No intervention | Participants will not receive hydroxyurea pretreatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of PBSC mobilization with G-CSF with or without hydroxyurea pretreatment in adults with beta thalassemia major
Measured: Measured at Month 2
Secondary outcomes (2)
Number of CD34+ stem/progenitor cells that are mobilized
Measured: 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: Measured at Year 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2006 (estimated)
- Study startJul 2006
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Beta-ThalassemiaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), George Papanicolaou Hospital
- Responsible party
- Sponsor
- Investigators
- George Stamatoyannopoulos, MD, DrSci, Study director, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00336362
- Sponsor's protocol ID
- 464
- Other IDs
- 2U01HL066947, IRB no. 27527, EudraCT no. 2005-000315-10
- Status last verified
- Dec 2012
- First submitted
- 12 Jun 2006
- Last updated
- 20 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess the Safety and Efficacy of G-CSF Mobilization With and Without Hydroxyurea Pretreatment in Adults With Beta Thalassemia Major
- ClinicalTrials.gov ID
- NCT00336362
- Acronym / sponsor ID
- 464
- Conditions
- Beta-Thalassemia
- Keywords
- Beta Thalassemia Major, Hematopoietic Stem Cell Mobilization, Gene Transfer Techniques
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), George Papanicolaou Hospital
- Study start
- Jul 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 13 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary Objective: To determine the safety of PBSC mobilization with G-CSF, with or without HU pretreatment in adults with beta thalassemia major.
Secondary Objective: To determine the number of CD34+ stem/progenitor cells that are mobilized under these conditions, as well as the ability of these cells to be transduced with a recombinant lentivirus vector for beta-globin and engraft immunodeficient mice.
Study Design: The ability of G-CSF to safely and effectively mobilize PBSC in adults with beta thalassemia major will be assessed in 12 splenectomized and 12 non-splenectomized patients. Of the 12 splenectomized patients, 6 will be treated with HU and G-CSF, and 6 will be treated only with G-CSF. Likewise, of the 12 non-splenectomized patients, 6 will be treated with HU and G-CSF, and 6 will be treated only with G-CSF. G-CSF mobilized participants will undergo leukapheresis on 2 consecutive days, with a target yield of 2 million CD34+ cells per kg of body weight. Safety will be assessed by monitoring for study-related toxicity. Efficacy will be assessed by measuring the total number of CD34+ cells, the ability of these cells to be transduced with a recombinant lentivirus vector for beta-globin, and the ability of these cells to engraft immunodeficient mice.
Population: Adults with beta thalassemia major.
Sample size: A total of 24 subjects will be enrolled: 12 splenectomized participants and 12 non-splenectomized participants.
End Points: This is a pilot study and no specific hypotheses are being tested. However, the study will allow for qualitative comparisons if outcomes between the various arms are markedly different. For example, the study will provide qualitative data on the safety and feasibility of utilizing HU and G-CSF to mobilize stem cells in individuals with beta thalassemia major. The study will be completed upon full enrollment, or when stopping criteria are met within specific study arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: HydroxyureaParticipants will receive hydroxyurea pretreatment. |
| 2 | No intervention | –Participants will not receive hydroxyurea pretreatment. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyureaAlso: hydreaHydroxyurea: 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. | Drug | 1 |
Primary outcome
Safety of PBSC mobilization with G-CSF with or without hydroxyurea pretreatment in adults with beta thalassemia major
Time frame: Measured at Month 2
2 secondary outcomes
Number of CD34+ stem/progenitor cells that are mobilized
Time frame: 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
Time frame: Measured at Year 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Stamatoyannopoulos, MD, DrSci study director
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydroxyurea in people with Beta-Thalassemia, run by University of Washington at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of PBSC mobilization with G-CSF with or without hydroxyurea pretreatment in adults with beta thalassemia major (time frame: Measured at Month 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2012.