Stem Cell Gene Therapy for Sickle Cell Disease

NCT02247843 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Lenti/βAS3-FB
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I clinical trial will assess the safety and initial evidence for efficacy of an autologous transplant of lentiviral vector modified peripheral blood for adults with severe sickle cell disease.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease (SCD); Gene Therapy; Lentiviral Vector; Beta Globin

Outcome Measures

Primary Outcomes (1)

• Evaluation of Safety

  1. Clinical toxicity: Absence of grade 3-4 SAEs 2. Absence of replication-competent lentivirus (RCL): 3. Absence of monoclonal expansion or leukoproliferative disorder from vector insertional effects: To monitor for monoclonal expansion or leukoproliferative complications, LAM-PCR will be performed. 4. Event-free survival. Event-free survival will be determined for each subject over the 24 months after gene therapy. An event is defined as death or performance of an allogeneic HSCT. 5. Absence of humoral immune response to novel epitopes of βAS3-globin protein

  up to 24 months

Study Arms (1)

βAS3-FB vector transduced peripheral blood CD34+ cells

EXPERIMENTAL

This is a single arm study without randomization. All subjects will receive the intervention of BetaAS3 lentiviral vector-modified autologous peripheral blood stem cell transplant.

Biological: βAS3-FB vector transduced peripheral blood CD34+ cells

Interventions

βAS3-FB vector transduced peripheral blood CD34+ cells BIOLOGICAL

CD34+ from the peripheral blood of patients with sickle cell disease (SCD) are transduced ex-vivo with the Lenti/βAS3-FB lentiviral vector. The transduced cells are then infused into the patient.

Also known as: Lenti/βAS3-FB

βAS3-FB vector transduced peripheral blood CD34+ cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 by time of enrollment
• Diagnosis of SCD documented by genetic analysis (S/S, S/β-thalassemia-zero)
• Must not have medically eligible and available HLA-identical sibling donor or 10/10 allele-matched unrelated donor (within a year prior to harvest) (or refuses to have an allogeneic HSCT)
• Inadequate clinical response to hydroxyurea (HU), defined as any one of the following outcomes, while on HU for at least 3 months:
• or more acute sickle pain crises requiring hospitalization
• no rise in Hb \>1.5 gm/dl from pre-HU baseline or requires transfusion to maintain Hb \> 6.0 gm/dL
• Has an episode of acute chest syndrome defined as development of a new pulmonary alveolar consolidation involving at least one complete lung segment associated with acute symptoms including: fever \>38.5, chest pain, tachypnea, intercostal retractions, nasal flaring, use of accessory muscles of respiration, wheezing, rales, or cough not attributable to asthma or bronchiolitis) in the preceding two year period prior to enrollment. The acute chest syndrome event occurred despite adequate supportive care measures.
• Or medical decision for other therapy (e.g. chronic transfusion program), or subject refusal to take HU.
• The patient must be off HU for at least 30 days (+/- 5 days) before PBSC collection.
• Must have one or more of the following clinical complications demonstrating disease severity:
• Clinically-significant neurologic event: stroke or any central nervous system deficit lasting \>24 hours.
• Abnormal head CT or brain MRI demonstrating previous stroke
• Administration of regular RBC transfusions for equal or longer than 1 year to prevent vaso- occlusive crises or other sickle cell disease complications or to maintain Hb \>6.
• Pulmonary arterial hypertension with tricuspid regurgitant jet velocity \> 2.5 m/sec within 1 year prior to enrollment
• At least one episode of acute chest syndrome that required hospitalization, within the 2 years prior to enrollment

You may not qualify if:

• Patient has a medically eligible and available HLA-identical sibling donor or 10/10 allele-matched unrelated donor (unless they refuse to have an allogeneic HSCT).
• Cardiac evaluation: left ventricular ejection fraction (LVEF) \< 40% or LV shortening fraction \< 26% by cardiac echocardiogram or by MUGA scan or clinically significant ECG abnormalities.
• Poorly controlled hypertension as determined by BP with systolic \>135 or diastolic \>95 mmHg despite treatment.
• Pulmonary evaluation: baseline oxygen saturation of \<85% or DLCO\< 40% (corrected for Hb)
• Renal evaluation: serum creatinine \>1.5x upper limit of normal for age or GFR\<60 mL/min/1.73 m2 within 90 days prior to PBSC collection.
• Hepatic evaluation: serum conjugated (direct) bilirubin \> 2x upper limit of normal for age as per local laboratory or ALT and AST \> 5 times upper limit of normal as per local laboratory within 90 days prior to PBSC collection.
• Hematologic evaluation: Leukopenia (WBC\< 3x103/uL) or neutropenia (ANC \< 1.0x103/uL) or thrombocytopenia (platelet count \< 100x103/uL) within 90 days prior to PBSC collection.
• PT/INR or PTT \>1.5x upper limit of normal or other clinically significant bleeding disorder to
• Liver Iron \>10mg/g by T2\* MRI (within 1 year prior to PBSC collection).
• Seropositivity for HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus), HTLV-1 (Human T-Lymphotropic Virus), or active Hepatitis B Virus, or active infection by CMV or parvovirus B19, based on positive blood PCR.
• Pregnancy
• Patient must not have any known cancer or other malignant disease or active infection by CT or MRI of head, chest or ultrasound of abdomen
• Abnormal karyotype by cytogenetic or other appropriate tests.

Sponsors & Collaborators

• Donald B. Kohn, M.D.: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (1)

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Romero Z, Urbinati F, Geiger S, Cooper AR, Wherley J, Kaufman ML, Hollis RP, de Assin RR, Senadheera S, Sahagian A, Jin X, Gellis A, Wang X, Gjertson D, Deoliveira S, Kempert P, Shupien S, Abdel-Azim H, Walters MC, Meiselman HJ, Wenby RB, Gruber T, Marder V, Coates TD, Kohn DB. beta-globin gene transfer to human bone marrow for sickle cell disease. J Clin Invest. 2013 Jul 1;123(8):3317-30. doi: 10.1172/JCI67930. Online ahead of print.

  PMID: 23863630 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Donald Kohn, MD

  University of California, Los Angeles

  STUDY CHAIR

• Gary Schiller, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 20, 2014
• First Posted: September 25, 2014
• Study Start: December 1, 2014
• Primary Completion: September 24, 2025
• Study Completion: September 24, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)