Recruiting
Phase 1

Gene Editing

Sponsor:

St. Jude Children's Research Hospital

Code:

NCT06506461

Conditions

Sickle Cell Disease

Eligibility Criteria

Sex: All

Age: 18 - 24

Healthy Volunteers: Not accepted

Interventions

Plerixafor

Busulfan

Gene-modified CD34+ cells

Motixafortide

Study Details

Brief 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.

Conditions

Sickle Cell Disease

Study ID

NCT06506461

Start date

Mar 21, 2025

Status verified date

Apr, 2026

Completion date

Dec, 2032

Anticipated

Primary completion date

Dec, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 24

Healthy Volunteers: Not accepted

Inclusion 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.

Exclusion Criteria:

  • 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 motixafortide 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.

Study Design

Enrollment

25 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Autologous, genetically modified CD34+ HSPCs Treatment

All eligible participants receive intervention as described in the Detailed Description with the following: motixafortide, plerixafor, busulfan, and autologous, gene-modified CD34+ cells

Interventions

Plerixafor

Given Subcutaneous (under the skin)

Busulfan

Given Intravenous (IV)

Gene-modified CD34+ cells

Given Intravenous (IV)

Motixafortide

Given Subcutaneous (under the skin)

Primary outcome measure

  • Incidence of neutrophil engraftment by day +42 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. [ Time Frame: Within 42 days of the cellular product infusion ]
  • Incidence of platelet engraftment by day +60 after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. [ Time Frame: 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. [ Time Frame: Within 1 year of the cellular product infusion ]
  • Frequency of off-target editing after infusion of the CRISPR/Cas9-edited CD34+ HSPCs. [ Time Frame: Within 3 years of the cellular product infusion ]
  • Occurrence of secondary graft failure, clonal hematopoiesis, MDS, or AML [ Time Frame: Within 3 years of the cellular product infusion ]

Central Contacts and Locations

Central contacts

Akshay Sharma, MBBS, MSc

888-226-4343referralinfo@stjude.org

Locations

St. Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Akshay Sharma, MBBS, MSc

888-226-4343referralinfo@stjude.org

More Information

Sponsor

St. Jude Children's Research Hospital

Last update posted

May 5, 2026

Last verified

Apr, 2026

Keywords

  • Plerixafor
  • Autologous
  • CD34+ cells
  • Apheresis
  • Conditioning
  • Busulfan
  • Gene Editing

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by St. Jude Children's Research Hospital on 2026-05-05.