Gene Transfer for Severe Combined Immunodeficiency, X-linked (SCID-X1) Using a Self-inactivating (SIN) Gammaretroviral Vector
|ClinicalTrials.gov Identifier: NCT01129544|
Recruitment Status : Active, not recruiting
First Posted : May 24, 2010
Last Update Posted : January 2, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Severe Combined Immunodeficiency||Biological: Gene transfer||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multi-institutional Phase I/II Trial Evaluating the Treatment of SCID-X1 Patients With Retrovirus-mediated Gene Transfer|
|Actual Study Start Date :||April 2010|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||March 2033|
Experimental: Gene Transfer
open label single arm study
Biological: Gene transfer
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.
- CD3 cell count post transfusion [ Time Frame: 6 Months Post Gene Transfer ]Immunological reconstitution defined as absolute CD3 cells of >300/μl and PHA stimulation index >15 at 6 months post infusion
- Incidence of life-threatening adverse reactions related to the gene therapy procedure. [ Time Frame: Up to 15 years post gene transfer ]Incidence of life-threatening adverse reactions related to the gene therapy procedure.
- Molecular characterization of gene transfer. [ Time Frame: Up to 15 years post gene transfer ]
- Ability to mount antibody responses to vaccination. [ Time Frame: Within 18 Months post standard vaccination to tentanus ]
- Normalization of nutritional status, growth, and development [ Time Frame: Up to 15 years post gene transfer ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01129544
|United States, California|
|Mattel Children's Hospital - UCLA|
|Los Angeles, California, United States, 90095|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02116|
|United States, Ohio|
|Cincinnati Children's Medical Center|
|Cincinnati, Ohio, United States, 45229|
|Principal Investigator:||Sung-Yun Pai, MD||Boston Children’s Hospital|