PHASE I/II CLINICAL TRIAL OF AUTOLOGOUS HEMATOPOIETIC STEM CELL GENE THERAPY FOR RAG1-DEFICIENT SEVERE COMBINED IMMUNODEFICIENCY

PHASE I/II CLINICAL TRIAL OF AUTOLOGOUS HEMATOPOIETIC STEM CELL GENE THERAPY FOR RAG1-DEFICIENT SEVERE COMBINED IMMUNODEFICIENCY - Phase I/II clinical trial on RAG1 gene therapy in SCID

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON54570

Enrollment

Registered

2019-07-25

Start date

2021-07-23

Completion date

Unknown

Last updated

2025-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

RAG1 SCID

Interventions

Patients will receive a single infusion of autologous CD34+ hematopoietic stem cells transduced with the pCCL.MND.coRAG1.wrpe lentiviral vector (RAG1 LV CD34+ cells).

Eligibility

Age

No minimum to 1 Years

Inclusion criteria

Inclusion criteria: - RAG1 deficient SCID as confirmed by genetic analysis - Peripheral blood T cells

Exclusion criteria

Exclusion criteria: - availability of a HLA-matched donor (i.c. HLA-identical sibling or 10/10 (A, B, C, DR, DQ) allele-matched (un)related donor) - RAG 1 deficiency with peripheral blood T cells > 300/µL and/or naïve T cells > 1/µL - Previous allogeneic stem cell transplantation - Significant organ dysfunction/co-morbidity (including but not limited to the ones listed below) a. Mechanical ventilation b. Shortening fraction on echocardiogram

Design outcomes

Primary

Measure	Time frame
The primary endpoints are feasibility based on the successful generation of an IMP meeting the release criteria for administration to RAG1 deficient SCID patients, and safety based on event free survival (EFS) after infusion of the IMP with events defined as a) infusion of unmanipulated backup stem cell product and/or allogeneic HSCT because of failure of hematological and/or immunological reconstitution after RAG1 LV cell infusion and b) occurrence of insertional mutagenesis presenting as malignant disease.	—

Measure

Time frame

The primary endpoints are feasibility based on the successful generation of an IMP meeting the release criteria for administration to RAG1 deficient SCID patients, and safety based on event free survival (EFS) after infusion of the IMP with events defined as a) infusion of unmanipulated backup stem cell product and/or allogeneic HSCT because of failure of hematological and/or immunological reconstitution after RAG1 LV cell infusion and b) occurrence of insertional mutagenesis presenting as malignant disease.

—

Secondary

Measure	Time frame
Secondary endpoints are a) overall survival, b) efficacy by determining T cell reconstitution (CD3 T cells > 300/µL blood), thymic function (presence of naïve CD4 T cells) and T and B cell receptor molecular repertoire at one year and immunoglobulin substitution dependence at two years after infusion of the RAG1 LV CD34+ cells, and vector copy numbers in leukocyte subpopulations at one year, and c) clinical outcome by determining the rate of infections, recovery from failure to thrive, and quality of life.	—

Measure

Time frame

Secondary endpoints are a) overall survival, b) efficacy by determining T cell reconstitution (CD3 T cells > 300/µL blood), thymic function (presence of naïve CD4 T cells) and T and B cell receptor molecular repertoire at one year and immunoglobulin substitution dependence at two years after infusion of the RAG1 LV CD34+ cells, and vector copy numbers in leukocyte subpopulations at one year, and c) clinical outcome by determining the rate of infections, recovery from failure to thrive, and quality of life.

—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)