Gene Transfer for Patients With Sickle Cell Disease Using a Gamma Globin Lentivirus Vector: An Open Label Phase 1/2 Pilot Study


4 United States sites

1 Jamaica site


18 to 45 Years


Phase 1/Phase 2

Study type








About the study

The purpose of this Phase 1/2 study is to determine the feasibility and safety of stem cell
collection and gamma-globin gene transfer, and success of gene correction in subjects with
sickle cell disease

participation requirements

– Signed informed consent form.

– Has confirmed diagnosis of sickle cell disease (SCD)

– Has severe sickle cell disease, defined as one or more of the following:

1. Minimum of two episodes of clinically diagnosed acute chest syndrome (ACS)
requiring hospital admission, or one life threatening episode of ACS requiring
intensive care unit (ICU) admission for exchange transfusion and/or intubation,
or frequent ACS episodes which necessitate treatment with chronic transfusion

2. Frequent painful vaso-occlusive episodes (VOEs) which significantly interfere
with normal life activities, defined as a history of 2 or more severe acute
sickle pain events per year requiring additional treatment at a medical facility
outside of home pain management over the preceding 2-year period prior to study
enrollment, or that necessitate chronic transfusion therapy.

3. Subjects on chronic transfusion therapy for severe disease symptoms other than
those listed above, and which interfere with normal life activities.

– Has failed hydroxyurea therapy, was unable to tolerate hydroxyurea therapy, or has
actively made the choice to not take the recommended daily hydroxyurea advised for
severe disease (Note: must be off hydroxyurea therapy for 2 months prior to stem cell
collection). If refusing hydroxyurea, the subject must document that they have been
educated about the benefits and continue to refuse the treatment. Patients placed on
chronic transfusion therapy instead of hydroxyurea for severe disease are eligible.
Subjects unable to take hydroxyurea due to financial or safety monitoring constraints
are eligible.

– Has adequate functional status and organ function as determined at Screening.

participation restrictions

– Female subjects who are pregnant or lactating/breastfeeding.

– Female subjects who are not surgically sterile, postmenopausal or who refuse to
practice effective method of birth control as determined by the Investigator for one
year after receiving the study drug. Women must also agree not to breastfeed for 1
year after receiving the study drug.

– Any participant of reproductive potential who refuses to agree to use an appropriate
contraceptive method determined by the Investigator, for 1 year after receiving the
study drug.

– Patients with an active malignant disease or receiving treatment for any type of
cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of
the skin).

– Current diagnosis or history of hepatitis B, hepatitis C, or HIV.

– Has received another study drug within 30 days, or 5 half-lives of the last dose
(whichever is longer), prior to screening.

– Has severe obstruction, restriction or diffusion defect on pulmonary function tests.

– Has uncontrolled bacterial, viral or fungal infections within 1 month prior to
starting the conditioning part of the study. Subjects with fever should wait for
symptoms to resolve before starting the conditioning part of the study.

– Has a history of stroke or is at moderate to high risk of primary stroke (eg receiving
chronic transfusions or hydroxyurea for primary prevention of stroke; has severe
cerebral vasculopathy defined as moderate stenosis in >2 arterial segments; and/or has
sever stenosis/occlusion in ≤2 segments in the polygon of Willis or presence of
Moyamoya-like disease).

– Patients with alpha thalassemia sickle cell disease.

– Has previous liver biopsy showing cirrhosis, bridging hepatic fibrosis, or active
hepatitis; or has received chronic transfusions and has previous evidence of iron
overload and evidence of liver fibrosis by noninvasive liver imaging.

– Has a matched sibling donor, unless the subject has declined this option or this
option is not feasible. Documentation must be included as part of the informed consent
process for subjects who decline this option.

– Has a known hypersensitivity to any study treatments (e.g. melphalan, plerixafor).

Other protocol-defined inclusion-exclusion criteria may apply.


  • New York, New York, United States, Icahn School of Medicine at Mount Sinai, 10029
  • Charlotte, North Carolina, United States, Atrium Health, 28204
  • Cincinnati, Ohio, United States, Cincinnati Children's Hospital Medical Center, 45229
  • Philadelphia, Pennsylvania, United States, University of Pennsylvania, 19104
  • Kingston, Jamaica, Caribbean Institute for Health Research, University of the West Indies