St. Jude Autologous Genome Edited Stem Cells For Sickle Cell Disease-1

Official Summary

This study is being done to test the safety of a new treatment called gene editing in Sickle Cell Disease (SCD) patients and to see if a single dose of this genetically modified cellular product will increase the amount of a certain hemoglobin called fetal hemoglobin (HbF) and help reduce the symptoms of SCD. Primary Objective * To assess the safety of autologous infusion of clustered regularly interspaced palindromic repeats (CRISPR)/ CRISPR associated protein (Cas9)-edited CD34+ hematopoietic stem and progenitor cells (HSPCs) in patients with severe SCD. Secondary Objective * To assess the efficacy autologous infusion of CRISPR/Cas9 genome-edited CD34+ HSPCs into patients with severe SCD.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 25 participants

Interventions

• DRUG: Plerixafor — Given Subcutaneous (under the skin)
• DRUG: Busulfan — Given Intravenous (IV)
• BIOLOGICAL: Gene-modified CD34+ cells — Given Intravenous (IV)
• DRUG: Motixafortide — Given Subcutaneous (under the skin)

Primary Outcomes

• Incidence of neutrophil engraftment by day +42 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. (Within 42 days of the cellular product infusion)
• Incidence of platelet engraftment by day +60 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. (Within 60 days of the cellular product infusion)
• Sustenance of multi-lineage engraftment and polyclonal hematopoiesis as measured by counts of different clones of myeloid cells, T cells, B cells, and NK cells at 1 year after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. (Within 1 year of the cellular product infusion)
• Frequency of off-target editing after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. (Within 3 years of the cellular product infusion)
• Occurrence of secondary graft failure, clonal hematopoiesis, MDS, or AML (Within 3 years of the cellular product infusion)

Secondary Outcomes

• Estimate the change in the annualized rate of SCD-related vaso-occlusive events (such as pain crises and acute chest syndrome events), starting at 3 months after the infusion of autologous CRISPR/Cas9-edited CD34+ HSPCs. (From 3 months post the cellular product infusion to 3 years post infusion)
• Compare the change from baseline in the total blood hemoglobin concentration. (From time of screening to 3 years post infusion)
• Compare the change from baseline in the fraction of red blood cells (RBCs) containing HbF. (From time of screening to 3 years post infusion)
• Change in incidence of packed RBC transfusions. (Within 1 year prior to infusion and within 3 months to 1 year post infusion)

Trial Locations

• St. Jude Children's Research Hospital, Memphis, Tennessee, United States

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