Status:
COMPLETED
Stem Cell Gene Therapy for Sickle Cell Disease
Lead Sponsor:
Donald B. Kohn, M.D.
Collaborating Sponsors:
California Institute for Regenerative Medicine (CIRM)
Conditions:
Sickle Cell Disease
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
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 disea...
Detailed Description
Sickle cell disease (SCD) affects \~90,000 people in the U.S. who suffer significant neurological, lung, and kidney damage, as well as severe chronic pain episodes that adversely impact on quality of ...
Eligibility Criteria
Inclusion
- PARTICIPANT INCLUSION CRITERIA
- 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:
- 2 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
- At least 2 acute sickle pain crises requiring hospitalization within the 2 years prior to enrollment
- Severe osteonecrosis
- History of acute dactylitis during childhood
- Recurrent priapism (2 or more episodes)
- Karnofsky performance score ≥60%
- PARTICIPANT EXCLUSION CRITERIA
- 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.
Exclusion
Key Trial Info
Start Date :
December 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 24 2025
Estimated Enrollment :
4 Patients enrolled
Trial Details
Trial ID
NCT02247843
Start Date
December 1 2014
End Date
September 24 2025
Last Update
December 17 2025
Active Locations (1)
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1
University of California, Los Angeles (UCLA)
Los Angeles, California, United States, 90095