RECRUITING

Gene Editing For Sickle Cell Disease

Conditions

Sickle Cell Disease Plerixafor Autologous CD34+ cells Apheresis Conditioning Busulfan Gene Editing

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2025-02

Study Completion:2032-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06506461

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 24 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥18 years and ≤24.9 years. * Patients with SCD (Hb SS, Hb SB0 and Hb SB+ genotype) who have experienced EITHER (a) 2 or more SCD-related vaso-occlusive events (acute pain events, acute chest syndrome, priapism and splenic sequestration) per year in the 2-year period before screening, OR (b) administration of regular red blood cell (RBC) transfusions (≥8 transfusions in the 12 months preceding enrollment) EXCEPT if the RBC transfusions are being administered for primary or secondary stroke prevention and, in the opinion of the treating hematologist, cannot be safely discontinued after infusion of the gene modified drug product. * Failure, intolerance, or refusal of hydroxyurea therapy. * Patients must be eligible for autologous stem cell transplant as per investigator's judgment. * Females of childbearing potential (i.e., those who are post-menarchal with an intact uterus and at least 1 ovary, and those who are less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from start of mobilization through at least 6 months post-infusion. * Males must agree to use effective contraception from start of mobilization through at least 6 months post-infusion. * Patients should be willing to participate in an additional long-term follow-up study after completion of this trial.	* Availability of an human leukocyte antigen (HLA)-matched sibling who is willing and able to donate an appropriate graft for hematopoietic cell transplantation (HCT). * Karnofsky or Lansky performance score \< 80. * Pregnant, as confirmed by positive serum or urine pregnancy test within 14 days before enrollment (if female). * Breastfeeding. * Uncontrolled (undergoing appropriate treatment and with progression of clinical symptoms) or clinically significant bacterial, viral, or fungal infections within 1 month before enrollment. * Patients with confirmed Hepatitis B or Hepatitis C infections. * Patients with confirmed seropositivity or positive nucleic acid amplification test (NAAT) for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV). * Patients with a history of stroke. * Serum conjugated (direct) bilirubin \> 2× the upper limit of normal for age, or serum alanine transaminase (ALT) \> 3× the upper limit of normal for age as per the local laboratory. Participants with hyperbilirubinemia or elevated aspartate aminotransferase (AST) as the result of hyperhemolysis, or with a severe drop in hemoglobin post blood transfusion, are not excluded as long as these values downtrend and return to acceptable limits subsequently. * Left ventricular shortening fraction \< 25% or ejection fraction \< 45% by echocardiogram. * Estimated creatinine clearance less than 60 mL/min/1.73m\^2. * Diffusion capacity of carbon monoxide (DLCO) \< 50% (adjusted for hemoglobin) OR baseline oxygen saturation \< 85% in patients unable to perform pulmonary function tests. * Prior HCT or gene therapy. * Known hepatic cirrhosis, bridging hepatic fibrosis, or active hepatitis. Appropriate ultrasound or magnetic resonance (MR) imaging may be used to define the presence and degree of cirrhosis. Liver biopsy may be performed at the discretion of the attending physician or principal investigator if there are concerns regarding the presence of severe hepatic fibrosis or cirrhosis such that participation in this trial will not be in the patient's best interest. * Active known malignancy, myelodysplasia, abnormal cytogenetics, or immunodeficiency. * Patients with history of a significant bleeding disorder. * Cerebrovascular procedure within 6 months, including pial synangiosis for moyamoya. * Patients with history of untreated moyamoya disease or presence of moyamoya disease at screening that in the opinion of the investigator puts the subjects at the risk of bleeding. * Evidence of a pathogenic clonal variant in any candidate gene detected by a standard, licensed next-generation sequencing clinical assay for gene mutations associated hematological malignancies. * Patients with history of intolerance, contraindication, or known sensitivity to plerixafor or busulfan. Prior anaphylactic reaction with excipients of the proposed product. * Patients with participation in another clinical study with an investigational drug/product within 30 days of screening or fewer than 5 half-lives of the investigational agent whichever is longer from screening. * Patients with history of alloimmunization to RBC antigens and for whom the investigator anticipates that there will be insufficient RBC units available for the duration of the study.

Inclusion Criteria

Exclusion Criteria

* Age ≥18 years and ≤24.9 years.
* Patients with SCD (Hb SS, Hb SB0 and Hb SB+ genotype) who have experienced EITHER (a) 2 or more SCD-related vaso-occlusive events (acute pain events, acute chest syndrome, priapism and splenic sequestration) per year in the 2-year period before screening, OR (b) administration of regular red blood cell (RBC) transfusions (≥8 transfusions in the 12 months preceding enrollment) EXCEPT if the RBC transfusions are being administered for primary or secondary stroke prevention and, in the opinion of the treating hematologist, cannot be safely discontinued after infusion of the gene modified drug product.
* Failure, intolerance, or refusal of hydroxyurea therapy.
* Patients must be eligible for autologous stem cell transplant as per investigator's judgment.
* Females of childbearing potential (i.e., those who are post-menarchal with an intact uterus and at least 1 ovary, and those who are less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from start of mobilization through at least 6 months post-infusion.
* Males must agree to use effective contraception from start of mobilization through at least 6 months post-infusion.
* Patients should be willing to participate in an additional long-term follow-up study after completion of this trial.

* Availability of an human leukocyte antigen (HLA)-matched sibling who is willing and able to donate an appropriate graft for hematopoietic cell transplantation (HCT).
* Karnofsky or Lansky performance score \< 80.
* Pregnant, as confirmed by positive serum or urine pregnancy test within 14 days before enrollment (if female).
* Breastfeeding.
* Uncontrolled (undergoing appropriate treatment and with progression of clinical symptoms) or clinically significant bacterial, viral, or fungal infections within 1 month before enrollment.
* Patients with confirmed Hepatitis B or Hepatitis C infections.
* Patients with confirmed seropositivity or positive nucleic acid amplification test (NAAT) for human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV).
* Patients with a history of stroke.
* Serum conjugated (direct) bilirubin \> 2× the upper limit of normal for age, or serum alanine transaminase (ALT) \> 3× the upper limit of normal for age as per the local laboratory. Participants with hyperbilirubinemia or elevated aspartate aminotransferase (AST) as the result of hyperhemolysis, or with a severe drop in hemoglobin post blood transfusion, are not excluded as long as these values downtrend and return to acceptable limits subsequently.
* Left ventricular shortening fraction \< 25% or ejection fraction \< 45% by echocardiogram.
* Estimated creatinine clearance less than 60 mL/min/1.73m\^2.
* Diffusion capacity of carbon monoxide (DLCO) \< 50% (adjusted for hemoglobin) OR baseline oxygen saturation \< 85% in patients unable to perform pulmonary function tests.
* Prior HCT or gene therapy.
* Known hepatic cirrhosis, bridging hepatic fibrosis, or active hepatitis. Appropriate ultrasound or magnetic resonance (MR) imaging may be used to define the presence and degree of cirrhosis. Liver biopsy may be performed at the discretion of the attending physician or principal investigator if there are concerns regarding the presence of severe hepatic fibrosis or cirrhosis such that participation in this trial will not be in the patient's best interest.
* Active known malignancy, myelodysplasia, abnormal cytogenetics, or immunodeficiency.
* Patients with history of a significant bleeding disorder.
* Cerebrovascular procedure within 6 months, including pial synangiosis for moyamoya.
* Patients with history of untreated moyamoya disease or presence of moyamoya disease at screening that in the opinion of the investigator puts the subjects at the risk of bleeding.
* Evidence of a pathogenic clonal variant in any candidate gene detected by a standard, licensed next-generation sequencing clinical assay for gene mutations associated hematological malignancies.
* Patients with history of intolerance, contraindication, or known sensitivity to plerixafor or busulfan. Prior anaphylactic reaction with excipients of the proposed product.
* Patients with participation in another clinical study with an investigational drug/product within 30 days of screening or fewer than 5 half-lives of the investigational agent whichever is longer from screening.
* Patients with history of alloimmunization to RBC antigens and for whom the investigator anticipates that there will be insufficient RBC units available for the duration of the study.

Contacts and Locations

Study Contact

Akshay Sharma, MBBS, MSc

CONTACT

866-278-5833

referralinfo@stjude.org

Principal Investigator

Akshay Sharma, MBBS, MSc

PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Study Locations (Sites)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

United States

Collaborators and Investigators

Sponsor: St. Jude Children's Research Hospital

Akshay Sharma, MBBS, MSc, PRINCIPAL_INVESTIGATOR, St. Jude Children's Research Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02

Study Completion Date2032-12

Study Record Updates

Study Start Date2025-02

Study Completion Date2032-12

Terms related to this study

Keywords Provided by Researchers

Plerixafor
Autologous
CD34+ cells
Apheresis
Conditioning
Busulfan
Gene Editing

Additional Relevant MeSH Terms

Sickle Cell Disease