Wiskott-Aldrich SyndromePhase 1/2NCT01410825
Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome
A Phase 1/2 study testing Retrovirus-mediated gene transfer in people with Wiskott-Aldrich Syndrome, run by David Williams at 1 site in United States.
Trial summary
The Wiskott-Aldrich Syndrome (WAS) is an inherited disorder that results in defects of the blood and bone marrow. It affects boys because the genetic mistake is carried on the X chromosome. Normal people have blood cells called platelets that stop bleeding when blood vessels are damaged. Read more about this study
- Who is it for?
- Ages 3 months to 35 years, men only
- Conditions the study is for
- Wiskott-Aldrich Syndrome
- What is being tested?
- Retrovirus-mediated gene transfer
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Sep 2024
- Phase
- Phase 1/2
- 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 3 months to 35 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed molecular diagnosis by DNA sequencing and either
- absence of the WAS protein by flow cytometry OR
- clinical score 3-5
- Age 3 months to 35 years
- For subjects < 5 years of age:
- Lack of HLA-genotypically identical bone marrow donor.
Show all 21Show fewer
- Lack of a 9/10 or 10/10 molecularly HLA-matched unrelated donor after 3 months of searching.
- Lack of a 6/6 molecularly HLA-matched cord blood donor of adequate cell number after 3 months of searching
- For subjects 5 years of age or older:
- a.Lack of HLA-genotypically identical bone marrow donor.
- Subjects who have undergone allogeneic transplant previously must additionally have:
- Failure defined as <5% donor T cell engraftment and
- Contraindication to re-use of the same donor due to severe GVHD or non-availability.
- Parental/guardian/patient signed informed consent
- Willingness to return for follow-up during the 5 year study period.
- Adequate organ function and performance status
- Performance status ≥50% (Lansky play for age <16 years, Karnofsky for age ≥16 years)
- Left ventricular ejection fraction >40% or shortening fraction >25%
- Bilirubin ≤ 2.0 mg/dL
- Measured creatinine clearance or GFR by nuclear medicine study ≥40 ml/min/1.73 m2
- DLCO (corrected for hemoglobin), FEV1, FVC >50% of predicted; if age < 7 years, then oxygen saturation >92% on room air
Who cannot join
- Contraindication to bone marrow harvest, or to administration of conditioning medication.
- Known positive HIV serology or HIV nucleic acid testing.
- Other uncontrolled infection.
- Active malignancy other than EBV lymphoproliferative disease.
- Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics
- Congenital cardiac disease with congestive heart failure
Show all 12Show fewer
- Oxygen dependence at baseline
- Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful study completion. This may include but is not limited to:
- Severe deterioration of clinical condition after collection of cells but before infusion of transduced cells
- Documented refusal or inability of the family to return for scheduled visits
- Other concerns about unwillingness or inability to comply with protocol requirements
- Unforeseen rare circumstances such as sudden loss of legal guardianship
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02116
About this study
The Wiskott-Aldrich Syndrome (WAS) is an inherited disorder that results in defects of the blood and bone marrow. It affects boys because the genetic mistake is carried on the X chromosome. Normal people have blood cells called platelets that stop bleeding when blood vessels are damaged. Boys with WAS have low numbers of platelets that do not function correctly. Boys with WAS are thus at risk for severe life-threatening bleeding. A normal immune system is made of special blood cells called white blood cells, which protect against infection and also fight certain types of cancer. In WAS, these white blood cells don't work as well as they should, making these boys very susceptible to infections and to a form of blood cancer known as lymphoma. The abnormal white blood cells of patients with WAS also cause diseases such as eczema and arthritis. Although WAS can be mild, severe forms need treatment as early as possible to prevent life-threatening complications due to bleeding, infection and blood cancer.
Over the past decade, investigators have developed new treatments based on the investigators knowledge of the defective gene causing WAS. The investigators can now use genes as a type of medicine that will correct the problem in the patient's own bone marrow. The investigators call this process gene transfer. The procedure is very similar to a normal bone marrow transplant, in that the old marrow is killed off using chemotherapy, but is different because the patient's own bone marrow is given back after it is treated by gene transfer. This approach can be used even if the patient does not have any matched donors available and will avoid problems such as GVHD and rejection. The investigators wish to test whether this approach is safe and whether gene transfer will lead to the development of a healthy immune and blood system.
Read the detailed description
Wiskott-Aldrich syndrome (WAS) (OMIM 301000) is a rare X-linked immunodeficiency caused by mutations in a single gene, WAS, mapping to Xp11.22-Xp11.3 and coding for the Wiskott-Aldrich Syndrome Protein (WASP) 1. WASP is a critical regulator of actin signaling with expression limited to hematopoietic cells, and thus is required for multiple functions including T cell activation, dendritic cell migration and podosome formation, and B cell terminal development and function. WAS is characterized by microthrombocytopenia, recurrent infections, eczema and associated with a high incidence of auto-immunity and of lymphoid malignancies. Classic or severe WAS, is generally observed in patients with nonsense mutations or insertions/deletions resulting in frameshift or splice-site mutations or missense mutations and resulting in unstable protein 2. With few exceptions, WASP-negative patients have classical disease. Affected patients have a severely reduced life expectancy.
Currently, the only curative option for WAS patients is hematopoietic stem cell transplantation (HSCT). This treatment is most successful when an HLA-identical sibling or matched unrelated donor is available and results in correction of microthrombocytopenia and immune dysfunction, even when stable mixed chimerism occurs. However, even patients undergoing matched HSCT can suffer from considerable morbidity and mortality due to graft versus host disease (GVHD) and many patients lack an HLA-identical donor. The outcome of mismatched related HSCT is consistently poor with survival of approximately 50%. Gene transfer is an attractive alternative treatment for WAS. Successful gene transfer using autologous gene-corrected HSC would overcome clinical complications linked to GVHD and its treatment. Furthermore, in contrast to allogeneic HSCT, gene transfer would not be limited by the availability of compatible donors. Several lines of evidence indicate that partial reconstitution with gene corrected cells may be sufficient to ameliorate the disease.
We propose here a Pilot and Feasibility study of ex vivo gene transfer using a lentiviral vector (LV) to transduce autologous bone marrow derived CD34+ HSC. Cells will be infused into patients conditioned with cytoreductive chemotherapy. Our collaborating investigators in Europe have developed a LV encoding the human WAS cDNA under control of the WAS promoter and pseudotyped with the Vesicular Stomatitis Virus glycoprotein (VSVg) envelope. This w1.6_hWASP_WPRE (VSVg) LV (abbreviated as w1.6W) has been shown to be efficacious in both in vitro and in vivo preclinical models. Safety including cellular toxicity, insertional mutagenesis and tumor formation has been studied by a number of methods including: 1) a sensitive in vitro transformation assay, 2) toxicity studies in transduced human CD34+ cells, 3) examination of the insertional pattern in transduced murine cells, and 4) long-term observation and secondary transplant studies in mice. In the United States, we plan to enroll 5 boys with classic WAS who lack a matched related or unrelated donor. Parallel studies (not under our Investigational New Drug application) using the same LV produced in the same facility, Genethon, will be conducted in London, UK (5 subjects) and Paris, France (5 subjects). The primary objective will be to demonstrate feasibility and safety. The secondary objective will be to assess therapeutic efficacy.
- Conditions
- Wiskott-Aldrich Syndrome
- Being tested
- Retrovirus-mediated gene transfer
- Keywords
- WAS, Wiskott, Gene Transfer, Gene Therapy
- Medical subject headings
- Wiskott-Aldrich Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retrovirus-mediated gene transferBiological
Two procedures: 1) Bone marrow harvest from the patient's posterior iliac crests or collection of peripheral blood stem cells via apheresis procedure. 2) One time infusion of patient's transduced bone marrow cells.
| Study group | Role | What they receive |
|---|---|---|
| Gene transfer | Experimental | Open label single arm study Receives: Biological: Retrovirus-mediated gene transfer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of infusion of transduced cells
Safety of infusion of transduced cells as rescue of hematopoiesis after conditioning (hematopoietic recovery as assessed by absolute neutrophil count (ANC) above 0.5 x 109 /l for three consecutive days, achieved within 6 weeks following infusion).
Measured: 5 Years
Engraftment of genetically corrected T cells
Engraftment of genetically corrected T cells in peripheral blood (as assessed by evidence of vector sequences in >1% of CD3+ T cells) at 6 months.
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2011 (estimated)
- Study startJul 2011
- Primary completionSep 2024
- Study completionSep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Wiskott-Aldrich SyndromeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Williams
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Williams, Boston Children's Hospital
- Investigators
- Jennifer Whangbo, M.D., Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01410825
- Sponsor's protocol ID
- CHB-P00000148
- Status last verified
- Apr 2025
- First submitted
- 4 Aug 2011
- Last updated
- 14 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Labrosse R, Chu JI, Armant MA, Everett JK, Pellin D, Kareddy N, Frelinger AL, Henderson LA, O'Connell AE, Biswas A, Coenen-van der Spek J, Miggelbrink A, Fiorini C, Adhikari H, Berry CC, Cantu VA, Fong J, Jaroslavsky J, Karadeniz DF, Li QZ, Reddy S, Roche AM, Zhu C, Whangbo JS, Dansereau C, Mackinnon B, Morris E, Koo SM, London WB, Baris S, Ozen A, Karakoc-Aydiner E, Despotovic JM, Forbes Satter LR, Saitoh A, Aizawa Y, King A, Nguyen MAT, Vu VDU, Snapper SB, Galy A, Notarangelo LD, Bushman FD, Williams DA, Pai SY. Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Blood. 2023 Oct 12;142(15):1281-1296. doi: 10.1182/blood.2022019117.
PubMed 37478401
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome
- ClinicalTrials.gov ID
- NCT01410825
- Acronym / sponsor ID
- CHB-P00000148
- Conditions
- Wiskott-Aldrich Syndrome
- Keywords
- WAS, Wiskott, Gene Transfer, Gene Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- David WilliamsUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Sep 2024 (actual)
- Study completion
- Sep 2024 (actual)
- First posted
- 5 Aug 2011 (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.
The Wiskott-Aldrich Syndrome (WAS) is an inherited disorder that results in defects of the blood and bone marrow. It affects boys because the genetic mistake is carried on the X chromosome. Normal people have blood cells called platelets that stop bleeding when blood vessels are damaged. Boys with WAS have low numbers of platelets that do not function correctly. Boys with WAS are thus at risk for severe life-threatening bleeding. A normal immune system is made of special blood cells called white blood cells, which protect against infection and also fight certain types of cancer. In WAS, these white blood cells don't work as well as they should, making these boys very susceptible to infections and to a form of blood cancer known as lymphoma. The abnormal white blood cells of patients with WAS also cause diseases such as eczema and arthritis. Although WAS can be mild, severe forms need treatment as early as possible to prevent life-threatening complications due to bleeding, infection and blood cancer.
Over the past decade, investigators have developed new treatments based on the investigators knowledge of the defective gene causing WAS. The investigators can now use genes as a type of medicine that will correct the problem in the patient's own bone marrow. The investigators call this process gene transfer. The procedure is very similar to a normal bone marrow transplant, in that the old marrow is killed off using chemotherapy, but is different because the patient's own bone marrow is given back after it is treated by gene transfer. This approach can be used even if the patient does not have any matched donors available and will avoid problems such as GVHD and rejection. The investigators wish to test whether this approach is safe and whether gene transfer will lead to the development of a healthy immune and blood system.
Detailed description
Wiskott-Aldrich syndrome (WAS) (OMIM 301000) is a rare X-linked immunodeficiency caused by mutations in a single gene, WAS, mapping to Xp11.22-Xp11.3 and coding for the Wiskott-Aldrich Syndrome Protein (WASP) 1. WASP is a critical regulator of actin signaling with expression limited to hematopoietic cells, and thus is required for multiple functions including T cell activation, dendritic cell migration and podosome formation, and B cell terminal development and function. WAS is characterized by microthrombocytopenia, recurrent infections, eczema and associated with a high incidence of auto-immunity and of lymphoid malignancies. Classic or severe WAS, is generally observed in patients with nonsense mutations or insertions/deletions resulting in frameshift or splice-site mutations or missense mutations and resulting in unstable protein 2. With few exceptions, WASP-negative patients have classical disease. Affected patients have a severely reduced life expectancy.
Currently, the only curative option for WAS patients is hematopoietic stem cell transplantation (HSCT). This treatment is most successful when an HLA-identical sibling or matched unrelated donor is available and results in correction of microthrombocytopenia and immune dysfunction, even when stable mixed chimerism occurs. However, even patients undergoing matched HSCT can suffer from considerable morbidity and mortality due to graft versus host disease (GVHD) and many patients lack an HLA-identical donor. The outcome of mismatched related HSCT is consistently poor with survival of approximately 50%. Gene transfer is an attractive alternative treatment for WAS. Successful gene transfer using autologous gene-corrected HSC would overcome clinical complications linked to GVHD and its treatment. Furthermore, in contrast to allogeneic HSCT, gene transfer would not be limited by the availability of compatible donors. Several lines of evidence indicate that partial reconstitution with gene corrected cells may be sufficient to ameliorate the disease.
We propose here a Pilot and Feasibility study of ex vivo gene transfer using a lentiviral vector (LV) to transduce autologous bone marrow derived CD34+ HSC. Cells will be infused into patients conditioned with cytoreductive chemotherapy. Our collaborating investigators in Europe have developed a LV encoding the human WAS cDNA under control of the WAS promoter and pseudotyped with the Vesicular Stomatitis Virus glycoprotein (VSVg) envelope. This w1.6_hWASP_WPRE (VSVg) LV (abbreviated as w1.6W) has been shown to be efficacious in both in vitro and in vivo preclinical models. Safety including cellular toxicity, insertional mutagenesis and tumor formation has been studied by a number of methods including: 1) a sensitive in vitro transformation assay, 2) toxicity studies in transduced human CD34+ cells, 3) examination of the insertional pattern in transduced murine cells, and 4) long-term observation and secondary transplant studies in mice. In the United States, we plan to enroll 5 boys with classic WAS who lack a matched related or unrelated donor. Parallel studies (not under our Investigational New Drug application) using the same LV produced in the same facility, Genethon, will be conducted in London, UK (5 subjects) and Paris, France (5 subjects). The primary objective will be to demonstrate feasibility and safety. The secondary objective will be to assess therapeutic efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gene transfer | Experimental | Biological: Retrovirus-mediated gene transferOpen label single arm study |
Who may qualify
- Ages
- 3 months to 35 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Confirmed molecular diagnosis by DNA sequencing and either
- Age 3 months to 35 years
- For subjects < 5 years of age:
- For subjects 5 years of age or older:
- a.Lack of HLA-genotypically identical bone marrow donor.
Key exclusion criteria (12 listed)
- Contraindication to bone marrow harvest, or to administration of conditioning medication.
- Known positive HIV serology or HIV nucleic acid testing.
- Other uncontrolled infection.
- Active malignancy other than EBV lymphoproliferative disease.
- Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics
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 |
|---|---|---|
| Retrovirus-mediated gene transferTwo procedures: 1) Bone marrow harvest from the patient's posterior iliac crests or collection of peripheral blood stem cells via apheresis procedure. 2) One time infusion of patient's transduced bone marrow cells. | Biological | Gene transfer |
Primary outcome
Safety of infusion of transduced cells
Time frame: 5 Years
Safety of infusion of transduced cells as rescue of hematopoiesis after conditioning (hematopoietic recovery as assessed by absolute neutrophil count (ANC) above 0.5 x 109 /l for three consecutive days, achieved within 6 weeks following infusion).
Engraftment of genetically corrected T cells
Time frame: 5 Years
Engraftment of genetically corrected T cells in peripheral blood (as assessed by evidence of vector sequences in >1% of CD3+ T cells) at 6 months.
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 14 Aug 2025.
- Derived from this study: PubMed 37478401Labrosse R, Chu JI, Armant MA, Everett JK, Pellin D, Kareddy N, Frelinger AL, Henderson LA, O'Connell AE, Biswas A, Coenen-van der Spek J, Miggelbrink A, Fiorini C, Adhikari H, Berry CC, Cantu VA, Fong J, Jaroslavsky J, Karadeniz DF, Li QZ, Reddy S, Roche AM, Zhu C, Whangbo JS, Dansereau C, Mackinnon B, Morris E, Koo SM, London WB, Baris S, Ozen A, Karakoc-Aydiner E, Despotovic JM, Forbes Satter LR, Saitoh A, Aizawa Y, King A, Nguyen MAT, Vu VDU, Snapper SB, Galy A, Notarangelo LD, Bushman FD, Williams DA, Pai SY. Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Blood. 2023 Oct 12;142(15):1281-1296. doi: 10.1182/blood.2022019117.
- Individual participant dataSharing planned: Undecided
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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.
Jennifer Whangbo, M.D. principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Retrovirus-mediated gene transfer in people with Wiskott-Aldrich Syndrome, run by David Williams at 1 site in United States.
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 21 inclusion and 12 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 14 Aug 2025. 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 United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 infusion of transduced cells (time frame: 5 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 NCT01410825, which also lists 1 linked publication.
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 14 Aug 2025.