Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector

NCT01129544 | Completed Phase 1 Results DMC

• 1 other identifier: IND14067
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

Researchers are working on ways to treat SCID patients who don't have a matched brother or sister. One of the goals is to avoid the problems that happen with stem cell transplant from parents and unrelated people, such as repeat transplants, incomplete cure of the immune system, exposure to chemotherapy, and graft versus host disease. The idea behind gene transfer is to replace the broken gene by putting a piece of genetic material (DNA) that has the normal gene into the child's cells. Gene transfer can only be done if we know which gene is missing or broken in the patient. For SCID-X1, gene transfer has been done in the laboratory and in two previous clinical trials by inserting the normal gene into stem cells from bone marrow. The bone marrow is the "factory" inside the bones that creates blood and immune cells. So fixing the gene in the bone marrow stem cells should fix the immune problem, without giving chemotherapy and without risk of graft versus host disease, because the child's own cells are used, rather than another person's. Out of the 20 subjects enrolled in the two previous trials, 18 are alive with better immune systems after gene transfer. Two of the surviving subjects received gene corrected cells over 10 years ago. Gene transfer is still research for two reasons. One is that not enough children have been studied to tell if the procedure is consistently successful. Of the 20 children enrolled in the previous two trials, one child did not have correction of the immune system, and died of complications after undergoing stem cell transplant. The second important reason why gene transfer is research is that we are still learning about the side effects of gene transfer and how to do gene transfer safely. In the last two trials, 5 children have experienced a serious side effect. These children developed leukemia related to the gene transfer itself. Leukemia is a cancer of the white blood cells, a condition where a few white blood cells grow out of control. Of these children, 4 of the 5 have received chemotherapy (medication to treat cancer) and are currently in remission (no leukemia can be found by sensitive testing), whereas one died of gene transfer-related leukemia.

Conditions

Severe Combined Immunodeficiency

Keywords

Severe combined immunodeficiency; SCID; XSCID; SCID-X1

Outcome Measures

Primary Outcomes (2)

• CD3 Cell Count Post Infusion

  Immunological reconstitution defined as absolute CD3 cells of \>300/μl and PHA stimulation index \>15 at 6 months post infusion

  6 Months Post Gene Transfer

• Incidence of Life Threatening Adverse Reactions Related to the Gene Therapy Procedure

  Follow up time for each of the 8 enrolled patients is as follows: Patient #1 -12 yrs, Patient#2 -11 yrs, Patient #6- 9 yrs, Patient #7- 8 yrs, Patient #8 - 4.5 yrs. Patient #3 \& #5 failed primary endpoint and had allo transplant, Patient #4 retreated with Gene therapy and is 6 years post 2nd infusion.

  4.5-12 years post infusion of the gene therapy product

Study Arms (1)

Gene Transfer

EXPERIMENTAL

open label single arm study

Biological: Gene transfer

Interventions

Gene transfer BIOLOGICAL

Three procedures: 1) Bone marrow harvest from the patient's posterior iliac crests. 2.) Chemotherapy conditioning with Busulfan 3)One time infusion of patient's transduced bone marrow cells.

Gene Transfer

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of SCID-X1 based on immunophenotype (\<200 CD3+ autologous T cells, and confirmed by DNA sequencing)
• AND
• Lack an HLA identical (A, B, C, DR, DQ) related donor
• AND either one of the following:
• \. Patients in good clinical condition who do not have a readily available HLA identical (A,B,C,DR,DQ) unrelated donor (readily available defined as: a donor confirmed within 6 weeks of searching, with ability to transplant within 3 months of diagnosis).
• \. Patients with an active, therapy-resistant infection or other medical conditions that significantly increase the risk of allogeneic transplant. Examples of "therapy-resistant infections that significantly increase the risk of allogeneic transplant" include but are not limited to:
• interstitial pneumonia due to adenovirus or parainfluenzae virus.
• protracted diarrhea requiring total parenteral nutrition.
• disseminated BCG infection.
• virus-induced lymphoproliferative disease.
• any active opportunistic infection (eg, due to Pneumocystis jiroveci, cytomegalovirus,cryptosporidium) that does not improve on medical management.

You may not qualify if:

• No available molecular diagnosis confirming SCID-X1.
• Patients who have an available HLA-identical related donor.
• Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease
• Patients with evidence of infection with HIV-1
• Previous gene transfer
• Major (life-threatening) congenital anomalies. Examples of "major (life-threatening) congenital anomalies" include, but are not limited to: unrepaired cyanotic heart disease, hypoplastic lungs, anencephaly or other major CNS malformations, other severe non-repairable malformations of the gastrointestinal or genitourinary tracts that significantly impair organ function.
• Although the presentation of the disease may be variable in type, the severity of the immunodeficiency is uniform. The gene transfer protocol will be instituted in the place of haploidentical transplant for those patients who do not have a matched family donor or in whom an unrelated donor transplant is not indicated for the reasons specified above. Apart from the gene transfer protocol, the patients will not undergo additional procedures that would not form part of an equivalent haploidentical transplantation regimen, and will not receive conditioning chemotherapy.

Sponsors & Collaborators

• David Williams: lead
• Boston Children's Hospital: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of California, Los Angeles: collaborator

Study Sites (3)

Mattel Children's Hospital - UCLA

Los Angeles, California, 90095, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02116, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (2)

• Clarke EL, Connell AJ, Six E, Kadry NA, Abbas AA, Hwang Y, Everett JK, Hofstaedter CE, Marsh R, Armant M, Kelsen J, Notarangelo LD, Collman RG, Hacein-Bey-Abina S, Kohn DB, Cavazzana M, Fischer A, Williams DA, Pai SY, Bushman FD. T cell dynamics and response of the microbiota after gene therapy to treat X-linked severe combined immunodeficiency. Genome Med. 2018 Sep 28;10(1):70. doi: 10.1186/s13073-018-0580-z.

  PMID: 30261899 DERIVED

• Hacein-Bey-Abina S, Pai SY, Gaspar HB, Armant M, Berry CC, Blanche S, Bleesing J, Blondeau J, de Boer H, Buckland KF, Caccavelli L, Cros G, De Oliveira S, Fernandez KS, Guo D, Harris CE, Hopkins G, Lehmann LE, Lim A, London WB, van der Loo JC, Malani N, Male F, Malik P, Marinovic MA, McNicol AM, Moshous D, Neven B, Oleastro M, Picard C, Ritz J, Rivat C, Schambach A, Shaw KL, Sherman EA, Silberstein LE, Six E, Touzot F, Tsytsykova A, Xu-Bayford J, Baum C, Bushman FD, Fischer A, Kohn DB, Filipovich AH, Notarangelo LD, Cavazzana M, Williams DA, Thrasher AJ. A modified gamma-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med. 2014 Oct 9;371(15):1407-17. doi: 10.1056/NEJMoa1404588.

  PMID: 25295500 DERIVED

MeSH Terms

Conditions

Severe Combined Immunodeficiency; X-Linked Combined Immunodeficiency Diseases

Interventions

Genetic Engineering

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Genetic Techniques; Investigative Techniques

Results Point of Contact

• Title: David Williams, MD
• Organization: Boston Children's Hospital

David.Williams2@childrens.harvard.edu

617-919-2697

Study Officials

• Jennifer Whangbo, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 21, 2010
• First Posted: May 24, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: April 21, 2026
• Results First Posted: April 21, 2026

Record last verified: 2026-03

Locations

US (3)