Status:
ACTIVE_NOT_RECRUITING
A Gene Transfer Study Inducing Fetal Hemoglobin in Sickle Cell Disease (GRASP, BMT CTN 2001)
Lead Sponsor:
David Williams
Collaborating Sponsors:
National Heart, Lung, and Blood Institute (NHLBI)
California Institute for Regenerative Medicine (CIRM)
Conditions:
Sickle Cell Disease
Eligibility:
All Genders
13-40 years
Phase:
PHASE2
Brief Summary
A promising approach for the treatment of genetic diseases is called gene therapy. Gene therapy is a relatively new field of medicine in which genetic material (mostly DNA) in the patient is changed t...
Detailed Description
This is an open-label, non-randomized, multi-center, phase 2 study involving a single infusion of autologous bone marrow derived CD34+ HSC cells transduced with the lentiviral vector containing a shor...
Eligibility Criteria
Inclusion
- A diagnosis of sickle cell disease with genotype HbSS or HbS/β0 thalassemia.
- Between the age of 13-40 years.
- Clinically severe disease, defined as at least 4 vaso-occlusive events (VOEs) within the past 24 months prior to consent.
- Adequate hematologic parameters (regardless of therapy) including white blood cell (WBC) count within the range of 2.5 - 25.0 x 10\^9 /L, hemoglobin within the range of 5 - 11 g/dL, and platelet count above 150 x 10\^9 /L
- Adequate organ function and performance status:
- Karnofsky/Lansky performance status ≥80%.
- Serum creatinine \</= 1.5 times the upper limit of normal for age, and calculated creatinine clearance or GFR \>/= 60 mL/min/1.73 m2.
- Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value \<3× the upper limit of normal (ULN).
- DLCO, FEV1, and FVC \>50% of predicted
- Left ventricular ejection fraction \>40% or shortening fraction \>25%
- No HLA-genotypically identical related bone marrow donor available.
- Parental/guardian/patient signed informed consent.
Exclusion
- Subjects who have:
- Concomitant condition or illness including: ongoing or active infection, active malignancy, major surgery in the past 30 days, medical/psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.
- Receiving a chronic transfusion regimen for primary or secondary stroke prophylaxis. (Note: patients with a history of abnormal TCD who have transitioned from transfusions to hydroxyurea for stroke prophylaxis are also not eligible for the study.)
- Patients with history of abnormal TCD (measured with a timed average maximum mean velocity of ≥200 cm/second in the terminal portion of the internal carotid or proximal portion of middle cerebral artery or if the imaging TCD method is used, \>185 cm/second plus evidence of intracranial vasculopathy) who were ever on transfusions and subsequently transitioned to hydroxyurea.
- History of overt stroke or any neurologic event lasting \>24 hours. (Note: patients with imaging evidence of silent stroke but not on a chronic transfusion regimen are not excluded.)
- Isolated recurrent priapism unresponsive to medical and surgical therapies in the absence of other qualifying VOE complications that meet inclusion criteria.
- Contraindication to administration of conditioning medication (busulfan)
- Prior allogeneic hematopoietic stem cell transplant
- Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics
- Severe cerebral vasculopathy
- Liver MRI (≤ 180 days prior to initiation of BU conditioning) to document hepatic iron content is required for participants who have received ≥20 packed red blood cell transfusions (cumulative); participants who have hepatic iron content ≥ 9 mg Fe/g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis, and active hepatitis (≤ 180 days prior to initiation of transplant conditioning); the absence of bridging fibrosis will be determined using the histological grading and staging scale as described by Ishak and colleagues (1995) as described in the Manual of Operations (MOO);
- Evidence of HIV infection, HTLV infection, active hepatitis B infection or active hepatitis C infection.
- Known acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on prior biopsy
- Receipt of an investigational study drug or procedure within 90 days of study enrollment
- Either or both of the following findings on screening bone marrow aspirate/biopsy: a) diagnosis of myelodysplastic syndrome (MDS) based on morphology and/or cytogenetics (based on WHO definitions) OR b) pathogenic mutation in any gene on the Rapid Heme Panel (RHP), a next-generation sequencing clinical assay for gene mutations associated with hematologic malignancies performed at Brigham and Women's Hospital.
- Pregnancy or breastfeeding
- Presence of a genetically-determined hypercoagulable state or personal history of prior VTE (deep vein thrombosis or pulmonary embolism) that would represent a contraindication to proceed with central line placement and study events.
- The Phase 2 trial is not enrolling patients who reside outside the US at this time.
Key Trial Info
Start Date :
July 12 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2027
Estimated Enrollment :
25 Patients enrolled
Trial Details
Trial ID
NCT05353647
Start Date
July 12 2022
End Date
July 1 2027
Last Update
April 18 2025
Active Locations (9)
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1
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
2
UCLA Medical Center
Los Angeles, California, United States, 90095
3
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States, 94609
4
UC Davis Medical Center
Sacramento, California, United States, 95817