Gene Editing For Sickle Cell Disease
NCT Number: NCT06506461
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Sickle Cell Disease
Interventions: DRUG: Plerixafor|DRUG: Busulfan|DRUG: Gene-modified CD34+ cells
Sponsor: St. Jude Children's Research Hospital
Sex: ALL
Age: ADULT
Enrollment: 25
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2031-12
Locations: St. Jude Children's Research Hospital, Memphis, Tennessee, 38105, United States

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.

Primary Outcome Measures: Incidence of neutrophil engraftment by day +42 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs., Upon completion of the trial, summary statistics will be computed for the time to neutrophil engraftment., Within 42 days of the cellular product infusion|Incidence of platelet engraftment by day +60 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs., Upon completion of the trial, summary statistics will be computed for the time to platelet engraftment., 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., Sustenance of multi-lineage engraftment will be described using descriptive statistics., Within 1 year of the cellular product infusion|Frequency of off-target editing after infusion of the CRISPR/Cas9-edited CD34+ HSPCs., Frequency of off-target editing will be described using descriptive statistics., Within 3 years of the cellular product infusion|Occurrence of secondary graft failure, clonal hematopoiesis, MDS, or AML, Occurrence will be described using descriptive statistics., Within 3 years of the cellular product infusion
Secondary Outcome Measures: 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., We will evaluate the change in the annualized rate of SCD-related vaso-occlusive events starting at 3 months after the infusion of autologous gene-edited CD34+ HSPCs relative to the annualized rate calculated during the 2-year period before study enrollment. The changes will be summarized using descriptive statistics and displayed graphically., From 3 months post the cellular product infusion to 3 years post infusion|Compare the change from baseline in the total blood hemoglobin concentration., The change from baseline (at the time of screening) in the total blood hemoglobin concentration will be calculated at various timepoints as described in the protocol. The changes will be summarized using descriptive statistics and displayed graphically., From time of screening to 3 years post infusion|Compare the change from baseline in the fraction of red blood cells (RBCs) containing HbF., The change from baseline (at the time of screening) in the fraction of RBCs containing HbF by immunostaining will be calculated at various timepoints as described in the protocol. The changes will be summarized using descriptive statistics and displayed graphically., From time of screening to 3 years post infusion|Change in incidence of packed RBC transfusions., The change from baseline (at the time of screening) in the incidence of packed RBC transfusions will be calculated at various timepoints as described in the protocol. The changes will be summarized using descriptive statistics and displayed graphically., Within 1 year prior to infusion and within 3 months to 1 year post infusion