Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome

NCT01410825 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CHB-P00000148
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Wiskott-Aldrich Syndrome

Keywords

WAS; Wiskott; Gene Transfer; Gene Therapy

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  5 Years

Study Arms (1)

Gene transfer

EXPERIMENTAL

Open label single arm study

Biological: Retrovirus-mediated gene transfer

Interventions

Retrovirus-mediated gene transfer BIOLOGICAL

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.

Gene transfer

Eligibility Criteria

• Age: 3 Months - 35 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• David Williams: lead

Study Sites (1)

Children's Hospital Boston

Boston, Massachusetts, 02116, United States

Location

Related Publications (1)

• 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.

  PMID: 37478401 DERIVED

MeSH Terms

Conditions

Wiskott-Aldrich Syndrome

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Jennifer Whangbo, M.D.

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief of the Division of Hematology/Oncology

Study Record Dates

• First Submitted: August 4, 2011
• First Posted: August 5, 2011
• Study Start: July 1, 2011
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: August 14, 2025

Record last verified: 2025-04

Locations

US (1)