Confirmed Diagnosis of ß-thalassemia MajorPhase 1NCT01639690

ß-Thalassemia Major With Autologous CD34+ Hematopoietic Progenitor Cells Transduced With TNS9.3.55 a Lentiviral Vector Encoding the Normal Human ß-Globin Gene

A Phase 1 study testing Autologous CD34+ cells transduced with TNS9.3.55 in people with Confirmed Diagnosis of ß-thalassemia Major, run by San Rocco Therapeutics at 1 site in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

Search all trials

Trial summary

The patient has inherited ß-thalassemia major through the genes. These genes have mistakes in them, so the body cannot make normal red blood cells. Stem cells are made in the bone marrow. They are the earliest form of blood cells. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Confirmed Diagnosis of ß-thalassemia Major
What is being tested?: Autologous CD34+ cells transduced with TNS9.3.55
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteItaly
Study dates: Jul 2012to Jul 2027
Phase: Phase 1
Are there results?: Not yet: the study is under way

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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 ß-thalassemia major and have been enrolled in a hypertransfusion program with a confirmed annual transfusion of ≥100 mL/kg/yr but < 200 mL/kg/yr, AND ≥ 8 transfusions of blood per year over a minimum of two years.
Patients must NOT have an HLA-matched sibling
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 ≥70% at the time of entry into the study.

Show all 20Show fewer

Subjects must have liver iron value of < 15 mg/g/dry weight Iron quantitation may be performed by imaging such as T2*MRI or by biopsy
Subjects must have no evidence of cirrhosis** of the liver. Fibrosis of the liver can be tested by Fibroscan (47, 48, 49), or by liver biopsy. These should be performed within approximately a one year period prior to entry onto the study.
Subjects with an evaluation of cardiac function indicating:
normal function on MUGA scan (Multiple Gated Acquisition scan) or other methodology.
And
Patients must have a left ventricular ejection fraction (LVEF) of ≥ 60% and/or T2*MRI cardiac evaluation with T2* ≥20 milliseconds
Subjects with asymptomatic pulmonary function based on Lung Diffusion Testing DLCO Test DLCO ≥ 50% of predicted (corrected for hemoglobin)
Subjects with a determination of renal function based on: serum creatinine < than or = to 1.5 mg/dL or if serum creatinine is outside the normal range, then CrCl > 60-ml/min/1.73 m2
Subjects must have adequate hepatic function based on:
< 3 x ULN ALT and
< 2.0 total serum bilirubin (unless secondary to hemolysis)
Patients must be available for follow-up evaluations at 30, 60, 180 days post BMT and yearly thereafter indefinitely.
The possibility of unrelated donor stem cell transplantation will be discussed with patients, and a "preliminary" search for an unrelated donor may be done at the request of the patient. However, the finding of a potential HLA-matched unrelated donor will not exclude the patient from participating into this trial).
As the inclusion criteria are more specific than the Lucarelli/Pesaro thalassemia pre-transplant classification (Class 1,2 or 3 according to presence or absence of fibrosis, adequate chelation and/or hepatomegaly), the criteria stated above will be used in lieu of the Lucarelli/Pesaro classification.

Who cannot join

Active infections including Hepatitis B and Hepatitis C***,
Active infections including HTLV 1 and 2, and HIV 1 and 2
Patients with treated HLTV or HIV
Diabetes Mellitus
Bone Marrow myelodysplasia and/or chromosomal abnormalities
Female patient pregnant or breast feeding

Show all 15Show fewer

Patients with uncontrolled seizure disorders
Patients with severe pulmonary hypertension Tricuspid Jet velocity > 2.5 m/sec
Family history of familial cancer syndromes (leukemia, breast, ovarian, colorectal, etc.)
Definition of active Hepatitis C include:
Positive HCV RNA Viral load by quantitative PCR testing Or if Negative HCV RNA viral load BUT on antiviral treatment
Liver biopsy with pathologic evidence of
Necrosis and inflammation around the portal areas - piecemeal necrosis or interface hepatitis or necrosis of hepatocytes and focal inflammation in the liver parenchyma.
Inflammatory cells in the portal areas ("portal inflammation").
Fibrosis, with early stages being confined to the portal tracts, intermediate stages being expansion of the portal tracts and bridging between portal areas or to the central area, and late stages being frank cirrhosis characterized by architectural disruption of the liver with fibrosis and regeneration.

Trial locations and contacts

1 site in 1 country.

Italy1 site

Hospital "V.Cervello" Uoc Ematologiaii E Malattie Rare
Palermo, 90146

Other trials in Italy

About this study

Official title: A Phase I Clinical Trial for the Treatment of ß-Thalassemia Major With Autologous CD34+ Hematopoietic Progenitor Cells Transduced With TNS9.3.55 a Lentiviral Vector Encoding the Normal Human ß-Globin Gene

This study is being done to see if the investigators can make the stem cells produce normal red blood cells and hemoglobin. The investigators do this by collecting the stem cells. The genes with mistakes are removed from the cells. These cells are then treated so they have the corrected gene for making normal hemoglobin. These treated cells are given back to the patient through an injection (shot) in the vein. This is also known as gene transfer. In order for the body to accept these cells, the patient will need to receive a low dose of a drug called busulfan. It is a drug that will prepare the body to receive the new stem cells.

This study will let the investigators know:

If it is safe to give the patient the treated stem cells
If the treated stem cells will go into the bone marrow without causing side effects.

Gene transfer has been used for the past five years. It has been successful in treating many blood disorders. At least 20 patients have received the type of treatment that the patient will get on this study. This treatment for B-thalassemia major was developed at Memorial Sloan Kettering (MSK). It was studied for a long time in the lab before being given to patients.

Conditions: Confirmed Diagnosis of ß-thalassemia Major
Being tested: Autologous CD34+ cells transduced with TNS9.3.55
Keywords: BUSULFAN, G-CSF, CliniMACS-CD34 Reagent System, Blood transfusion, 10-164, Autologous CD34+ cells transduced with TNS9.3.55, a lentiviral vector encoding the human β-globin gene

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Autologous CD34+ cells transduced with TNS9.3.55Genetic
Also called Patient treatment with Filgrastim will last for up to 6 days with apheresis, collection on days 4 and 5 or days 5 or 6 if required. Reduced Intensity Conditioning will, consist of two days of busulfan treatment with an interval of two days prior to transplantation., Intravenous infusion of autologous CD34+ cells transduced with TNS9.3.55 will
Patients will receive Filgrastim followed by apheresis of peripheral blood stem cells. CD34+ cells will be purified and transduced ex vivo. Transduced cells will be frozen in several aliquots whenever possible while vector copy number determination and biosafety testing are performed. Patients will be treated in the outpatient and/or inpatient units, and receive intravenous busulfan (8mg/kg) as non-myeloablative conditioning. Patients will be administered 2-12 x 10^6 transduced CD34+ cells per kg in 1 or several infusions. A back-up of 2 x 10^6 untransduced CD34+ cells per kg will be preserved for every patient.

Study groups in NCT01639690
Study group	Role	What they receive
Autologous CD34+ cells transduced with TNS9.3.55	Experimental	An open label study using a non-myeloablative conditioning regimen of busulfan and 1 or several infusions of autologous hematopoietic stem cells transduced with a lentiviral vector encoding the human ß-globin gene. Receives: Genetic: Autologous CD34+ cells transduced with TNS9.3.55

What is being measured

The primary outcome is the main question the study is designed to answer.

safety
of transplanted autologous CD34+ hematopoietic cells that are transduced ex vivo with TNS9.3.55 and transplanted in subjects with ß-thalassemia major conditioned with a reduced-intensity non-myeloablative preparative regimen.
1. The occurrence of insertional oncogenesis, which will be investigated by monitoring peripheral blood cell counts and leukocyte clonality using FACS analysis, qPCR for vector. copy number, LAM-PCR and/or 454 sequencing;
2. The generation of a replication-competent lentivirus (RCL).
3. The safety of a low dose non-myeloablative conditioning regimen
Measured: 2 years
tolerability
of transplanted autologous CD34+ hematopoietic cells that are transduced ex vivo with TNS9.3.55 \& transplanted in subjects with ß-thalassemia major conditioned with a reduced-intensity non-myeloablative preparative regimen. monitoring the following: 1. The occurrence of insertional oncogenesis, which will be investigated by monitoring peripheral blood cell counts \& leukocyte clonality using FACS analysis, qPCR for vector. copy number, LAM-PCR and/or 454 sequencing; 2.The generation of a replication-competent lentivirus (RCL). 3.The safety of a low dose non-myeloablative conditioning regimen
Measured: 2 years

Secondary outcomes (2)

the level of engraftment
of the genetically modified autologous CD34+ cells and expression of the transduced ß-globin gene as measured by: Blood for measurement of vector copy number and transgene expression in blood cells at months 1, 2 and 3.
- Bone Marrow Samples for evaluation of CFU, BFU-E gene+ colonies and Q-PCR will be tested at month 1.
Measured: 2 years
The frequency of post transplant palliative transfusions
The number of red blood cell transfusions after engraftment will be quantitatively evaluated for efficacy purposes.
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2012Jul 2027

First posted13 Jul 2012 (estimated)
Study startJul 2012
Primary completionJul 2027 (estimated)
Study completionJul 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Confirmed Diagnosis of ß-thalassemia MajorStudies of the same condition, open and under way.
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 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01639690
Sponsor's protocol ID: 10-164
Status last verified: Apr 2026
First submitted: 11 Jul 2012
Last updated: 24 Apr 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Boulad F, Maggio A, Wang X, Moi P, Acuto S, Kogel F, Takpradit C, Prockop S, Mansilla-Soto J, Cabriolu A, Odak A, Qu J, Thummar K, Du F, Shen L, Raso S, Barone R, Di Maggio R, Pitrolo L, Giambona A, Mingoia M, Everett JK, Hokama P, Roche AM, Cantu VA, Adhikari H, Reddy S, Bouhassira E, Mohandas N, Bushman FD, Riviere I, Sadelain M. Lentiviral globin gene therapy with reduced-intensity conditioning in adults with beta-thalassemia: a phase 1 trial. Nat Med. 2022 Jan;28(1):63-70. doi: 10.1038/s41591-021-01554-9. Epub 2022 Jan 3.
PubMed 34980909
Boulad F, Wang X, Qu J, Taylor C, Ferro L, Karponi G, Bartido S, Giardina P, Heller G, Prockop SE, Maggio A, Sadelain M, Riviere I. Safe mobilization of CD34+ cells in adults with beta-thalassemia and validation of effective globin gene transfer for clinical investigation. Blood. 2014 Mar 6;123(10):1483-6. doi: 10.1182/blood-2013-06-507178. Epub 2014 Jan 15.
PubMed 24429337

Study at a glance

From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Clinical Trial for the Treatment of ß-Thalassemia Major With Autologous CD34+ Hematopoietic Progenitor Cells Transduced With TNS9.3.55 a Lentiviral Vector Encoding the Normal Human ß-Globin Gene
ClinicalTrials.gov ID: NCT01639690
Acronym / sponsor ID: 10-164
Conditions: Confirmed Diagnosis of ß-thalassemia Major
Keywords: BUSULFAN, G-CSF, CliniMACS-CD34 Reagent System, Blood transfusion, 10-164, Autologous CD34+ cells transduced with TNS9.3.55, a lentiviral vector encoding the human β-globin gene
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 10 participants (estimated)
Lead sponsor: San Rocco TherapeuticsUniversity, hospital or other
Study start: Jul 2012
Primary completion: Jul 2027 (estimated)
Study completion: Jul 2027 (estimated)
First posted: 13 Jul 2012 (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.

This study will let the investigators know:

If it is safe to give the patient the treated stem cells
If the treated stem cells will go into the bone marrow without causing side effects.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Autologous CD34+ cells transduced with TNS9.3.55	Experimental	Genetic: Autologous CD34+ cells transduced with TNS9.3.55An open label study using a non-myeloablative conditioning regimen of busulfan and 1 or several infusions of autologous hematopoietic stem cells transduced with a lentiviral vector encoding the human ß-globin gene.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (20 listed)

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 ß-thalassemia major and have been enrolled in a hypertransfusion program with a confirmed annual transfusion of ≥100 mL/kg/yr but < 200 mL/kg/yr, AND ≥ 8 transfusions of blood per year over a minimum of two years.
Patients must NOT have an HLA-matched sibling
Patients must be off hydroxyurea (HU) or erythropoietin (EPO) treatment for at least three months prior to entry onto the study

Key exclusion criteria (15 listed)

Active infections including Hepatitis B and Hepatitis C***,
Active infections including HTLV 1 and 2, and HIV 1 and 2
Patients with treated HLTV or HIV
Diabetes Mellitus
Bone Marrow myelodysplasia and/or chromosomal abnormalities

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
Autologous CD34+ cells transduced with TNS9.3.55Also: Patient treatment with Filgrastim will last for up to 6 days with apheresis, collection on days 4 and 5 or days 5 or 6 if required. Reduced Intensity Conditioning will, consist of two days of busulfan treatment with an interval of two days prior to transplantation., Intravenous infusion of autologous CD34+ cells transduced with TNS9.3.55 willPatients will receive Filgrastim followed by apheresis of peripheral blood stem cells. CD34+ cells will be purified and transduced ex vivo. Transduced cells will be frozen in several aliquots whenever possible while vector copy number determination and biosafety testing are performed. Patients will be treated in the outpatient and/or inpatient units, and receive intravenous busulfan (8mg/kg) as non-myeloablative conditioning. Patients will be administered 2-12 x 10^6 transduced CD34+ cells per kg in 1 or several infusions. A back-up of 2 x 10^6 untransduced CD34+ cells per kg will be preserved for every patient.	Genetic	Autologous CD34+ cells transduced with TNS9.3.55

Primary outcome

safety
Time frame: 2 years
of transplanted autologous CD34+ hematopoietic cells that are transduced ex vivo with TNS9.3.55 and transplanted in subjects with ß-thalassemia major conditioned with a reduced-intensity non-myeloablative preparative regimen. 1. The occurrence of insertional oncogenesis, which will be investigated by monitoring peripheral blood cell counts and leukocyte clonality using FACS analysis, qPCR for vector. copy number, LAM-PCR and/or 454 sequencing; 2. The generation of a replication-competent lentivirus (RCL). 3. The safety of a low dose non-myeloablative conditioning regimen
tolerability
Time frame: 2 years
of transplanted autologous CD34+ hematopoietic cells that are transduced ex vivo with TNS9.3.55 \& transplanted in subjects with ß-thalassemia major conditioned with a reduced-intensity non-myeloablative preparative regimen. monitoring the following: 1. The occurrence of insertional oncogenesis, which will be investigated by monitoring peripheral blood cell counts \& leukocyte clonality using FACS analysis, qPCR for vector. copy number, LAM-PCR and/or 454 sequencing; 2.The generation of a replication-competent lentivirus (RCL). 3.The safety of a low dose non-myeloablative conditioning regimen

2 secondary outcomes

the level of engraftment
Time frame: 2 years
The frequency of post transplant palliative transfusions
Time frame: 2 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
Derived from this study: PubMed 34980909Boulad F, Maggio A, Wang X, Moi P, Acuto S, Kogel F, Takpradit C, Prockop S, Mansilla-Soto J, Cabriolu A, Odak A, Qu J, Thummar K, Du F, Shen L, Raso S, Barone R, Di Maggio R, Pitrolo L, Giambona A, Mingoia M, Everett JK, Hokama P, Roche AM, Cantu VA, Adhikari H, Reddy S, Bouhassira E, Mohandas N, Bushman FD, Riviere I, Sadelain M. Lentiviral globin gene therapy with reduced-intensity conditioning in adults with beta-thalassemia: a phase 1 trial. Nat Med. 2022 Jan;28(1):63-70. doi: 10.1038/s41591-021-01554-9. Epub 2022 Jan 3.
Derived from this study: PubMed 24429337Boulad F, Wang X, Qu J, Taylor C, Ferro L, Karponi G, Bartido S, Giardina P, Heller G, Prockop SE, Maggio A, Sadelain M, Riviere I. Safe mobilization of CD34+ cells in adults with beta-thalassemia and validation of effective globin gene transfer for clinical investigation. Blood. 2014 Mar 6;123(10):1483-6. doi: 10.1182/blood-2013-06-507178. Epub 2014 Jan 15.
San Rocco TherapeuticsLink provided by the sponsor.

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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous CD34+ cells transduced with TNS9.3.55 in people with Confirmed Diagnosis of ß-thalassemia Major, run by San Rocco Therapeutics at 1 site in Italy.

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 20 inclusion and 15 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: under way, not looking for participants, as of the sponsor's last update on 24 Apr 2026. 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 Italy. 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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 (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01639690, which also lists 2 linked publications.

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 24 Apr 2026.