Severe Combined Immunodeficiency Disease, X-linked Clinical Trial
— LVXSCID-NDOfficial title:
A Pilot Feasibility Study of Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector to Transduce Autologous CD34+ Hematopoietic Cells
| Verified date | April 2024 |
| Source | St. Jude Children's Research Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
SCID-X1 is a genetic disorder of blood cells caused by DNA changes in a gene that is required for the normal development of the human immune system. The purpose of this study is to determine if a new method, called lentiviral gene transfer, can be used to treat SCID-X1. This method involves transferring a normal copy of the common gamma chain gene into the participant's bone marrow stem cells. The investigators want to determine if the procedure is safe, whether it can be done according to the methods they have developed, and whether the procedure will provide a normal immune system for the patient. It is hoped that this type of gene transfer may offer a new way to treat children with SCID-X1 that do not have a brother or sister who can be used as a donor for stem cell transplantation.
| Status | Suspended |
| Enrollment | 28 |
| Est. completion date | August 2034 |
| Est. primary completion date | August 2025 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | N/A to 24 Months |
| Eligibility | Inclusion Criteria: * Treatment Eligibility Criteria: - Age <2 years at the time of enrollment. - No prior therapy with allogeneic stem cell transplantation. - A clinical diagnosis of SCID-X1 documented in the medical record. - A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA. - Age > 2 months to < 1 year of age at the time of busulfan administration. - Less than 300 CD3+ T-cells by flow cytometry or higher if evidence of maternal engraftment as supported by peripheral blood FISH analysis for XY and XX. - Lymphocyte proliferation to phytohemagglutinin (PHA) <10% of the lower limit of normal for the laboratory. Treatment Exclusion Criteria: - Availability of a HLA matched sibling for allogeneic transplantation - Prior therapy with allogeneic stem cell transplantation - Positive for HIV infection by genome PCR - Presence of a medical condition indicating that survival will be less than 16 weeks such as the requirement for mechanical ventilation, severe failure of a major organ system, or evidence of a serious, progressive infection that is refractory to medical therapy. - The presence of any medical contraindications to general anesthesia and bone marrow harvest by aspiration - A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care. |
| Country | Name | City | State |
|---|---|---|---|
| United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
| United States | University of California-San Francisco | San Francisco | California |
| United States | Seattle Children's Research Institute | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| St. Jude Children's Research Hospital | Assisi Foundation, California Institute for Regenerative Medicine (CIRM), National Heart, Lung, and Blood Institute (NHLBI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Pharmacokinetic (PK) variables of busulfan | Blood collections for pharmacokinetic sampling will be performed with dose 1 and used to determine dose modifications for dose 2, if needed. The specific times for blood collects will be institution specific. Summary statistics will be reported. | Days -2 and -1 prior to therapy | |
| Other | Number of patients who achieve the desired therapeutic busulfan AUC | The efficacy of busulfan dose-targeting with busulfan administration every 24 hours for a total of 2 doses in order to achieve a cumulative busulfan AUC of 22 mg*hr/L will be evaluated. The number of patients who achieve the desired therapeutic busulfan AUC will be reported | Day 0 | |
| Other | B-cell function evaluated by Immune response | Evaluation may include ?c expression in circulating B-cells, measurement of serum IgG, IgA, and IgM concentration, measurement of antibody responses to vaccination, evaluation of IgG production after cessation of intravenous gamma globulin therapy in patients with clinical indications to discontinue IVIG. Summary statistics will be reported. | 52 weeks post gene transfer | |
| Other | Number of NK cells | Evaluation will include flow cytometry evaluation of NK cell numbers. Summary statistics will be reported. | 52 weeks post gene transfer | |
| Other | Vector copy number by location of vector-integration sites in sorted blood cells | Sorted T-cells, B-cells, NK cells, granulocytes and monocytes will be evaluated for vector copy number. Studies on sorted cells will also include deep sequencing with an automated sequencer to characterize insertion sites, and expression array analysis of T-cell clones to assay for gene expression alterations within 100 kb of the insertion sites. Summary statistics will be reported. | up to 10 years post gene transfer | |
| Other | Event-free survival (EFS) | Event is defined as death, requiring boost post infusion, or an oncogenic event . EFS is defined as time from busulfan infusion to event defined here with all patients surviving at the time of analysis censored. | from baseline up to 10 years post gene transfer | |
| Other | Overall survival (OS) | OS is defined as time from busulfan infusion to death with all patients surviving at the time of analysis censored. | up to 10 years post gene transfer | |
| Primary | Number of patients with adequate cell collection and processing | The number of patients who underwent no more than two bone marrow harvests and cryopreservation of at least 1.0 million cells/kg following vector transduction. | Day 0 | |
| Primary | Number of patients with adequate neutrophil count recovery after busulfan conditioning | Adequate recovery is defined as absolute neutrophil count (ANC) >500 cells/µl by day +42 unless the patient is neutropenic prior to busulfan administration. | Day 42 post gene transfer | |
| Primary | Number of patients without Grade 4 adverse event (AE) | The number of patients experiencing no directly related grade 4 or greater adverse event. | 42 days post gene transfer | |
| Primary | Number of patients with successful reconstitution | Reconstitution with transduced cells defined as detection of vector-marked peripheral blood cells by real time PCR at or above 0.02% VCN in total WBC. | 42 days post gene transfer | |
| Primary | Number of patients with treatment failure | Treatment failure will be defined as lack of adequate cell collection and processing, lack of neutrophil count recovery by day +42, occurrence of grade 4 or greater toxicities by day +42, and/or lack of detection of >0.02% transduced cells in peripheral blood by day +42 post gene transfer. | 42 days post gene transfer |