Autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a for Anemia, Sickle Cell

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Medical College of Wisconsin, Milwaukee, WI
Anemia, Sickle Cell+1 More
Autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a - Biological
Eligibility
< 65
All Sexes
What conditions do you have?
Select

Study 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 to treat his or her own disease. In gene therapy, we introduce new genetic material in order to fix or replace the patient's disease gene, with the goal of curing the disease. The procedure is similar to a bone marrow transplant, in that the patient's malfunctioning blood stem cells are reduced or eliminated using chemotherapy, but it is different because instead of using a different person's (donor) blood stem cells for the transplant, the patient's own blood stem cells are given back after the new genetic material has been introduced into those cells. This approach has the advantage of eliminating any risk of graft versus host disease (GVHD), reducing the risk of graft rejection, and may also allow less chemotherapy to be utilized for the conditioning portion of the transplant procedure. To introduce new genetic material into the patient's own blood stem cells we use a modified version of a virus (called a 'vector') that efficiently inserts the "correcting" genetic material into the cells. The vector is a specialized biological medicine that has been formulated for use in human beings. Fetal hemoglobin (HbF) is a healthy, non-sickling kind of hemoglobin. The investigators have discovered a gene that is very important in controlling the amount of HbF. Decreasing the expression of this gene in sickle cell patients could increase the amount of fetal hemoglobin while simultaneously reducing the amount of sickle hemoglobin in their blood, specifically the amount in red blood cells where sickle hemoglobin causes damage to the cell, and therefore potentially cure or significantly improve the condition. The gene we are targeting for change in this study that controls the level of fetal hemoglobin is called BCL11A. In summary, the advantages of a gene therapy approach include: 1) it can be used even if the patient does not have a matched donor available; 2) it may allow a reduction in the amount of chemotherapy required to prepare the patient for the transplant; and 3) it will avoid certain strong medicines often required to prevent and treat GVHD and rejection. Our lab studies with normal mice, mice that have a form of SCD, and with cells from the bone marrow of SCD patients who have donated bone marrow for research purposes show this approach is very effective in reducing the amount of sickle hemoglobin in red cells. Our pilot trial testing this approach in 10 patients with SCD has shown that the treatment has not caused any unexpected safety problems, and that it increases HbF within the red blood cells. Our goal is to continue to test whether this approach is safe, and whether using gene therapy to change the expression of BCL11A will lead to decreased episodes of vaso-occlusive crisis pain in people with SCD.

Eligible Conditions

  • Anemia, Sickle Cell

Treatment Effectiveness

Study Objectives

1 Primary · 5 Secondary · Reporting Duration: 24 months prior to consent and 6 months to 24 months post-infusion of gene modified cells

Month 24
Percentage change in the annualized number of VOEs
Month 24
Hemoglobin Function
Month 18
Occurrence of VOEs by Month 18 post-infusion
Month 24
Occurrence of VOEs by Month 24 post-infusion
Month 24
Toxicities and Adverse Events
Month 18
Hemolysis

Trial Safety

Trial Design

1 Treatment Group

Treatment Arm
1 of 1
Experimental Treatment

25 Total Participants · 1 Treatment Group

Primary Treatment: Autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a · No Placebo Group · Phase 2

Treatment Arm
Biological
Experimental Group · 1 Intervention: Autologous CD34+ HSC cells transduced with the lentiviral vector containing a shRNA targeting BCL11a · Intervention Types: Biological

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 24 months prior to consent and 6 months to 24 months post-infusion of gene modified cells
Closest Location: Medical College of Wisconsin · Milwaukee, WI
Photo of medical college of wisconsin 1Photo of medical college of wisconsin 2Photo of medical college of wisconsin 3
2006First Recorded Clinical Trial
11 TrialsResearching Anemia, Sickle Cell
560 CompletedClinical Trials

Who is running the clinical trial?

David WilliamsLead Sponsor
4 Previous Clinical Trials
33 Total Patients Enrolled
1 Trials studying Anemia, Sickle Cell
10 Patients Enrolled for Anemia, Sickle Cell
National Heart, Lung, and Blood Institute (NHLBI)NIH
3,555 Previous Clinical Trials
46,915,164 Total Patients Enrolled
148 Trials studying Anemia, Sickle Cell
46,498 Patients Enrolled for Anemia, Sickle Cell
California Institute for Regenerative Medicine (CIRM)OTHER
57 Previous Clinical Trials
3,034 Total Patients Enrolled
3 Trials studying Anemia, Sickle Cell
12 Patients Enrolled for Anemia, Sickle Cell
bluebird bioIndustry Sponsor
18 Previous Clinical Trials
1,792 Total Patients Enrolled
7 Trials studying Anemia, Sickle Cell
1,373 Patients Enrolled for Anemia, Sickle Cell
Blood and Marrow Transplant Clinical Trials NetworkNETWORK
48 Previous Clinical Trials
14,002 Total Patients Enrolled
4 Trials studying Anemia, Sickle Cell
2,063 Patients Enrolled for Anemia, Sickle Cell

Eligibility Criteria

Age < 65 · All Participants · 10 Total Inclusion Criteria

Mark “yes” if the following statements are true for you:
You have no HLA-genotypically identical related bone marrow donor available.
You have vaso-occlusive disease (VOD) and you are 18 years or older.
You have hematologic parameters 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.
You have a left ventricular ejection fraction of 40% or a shortening fraction of 25% or both.

About The Reviewer

Michael Gill preview

Michael Gill - B. Sc.

First Published: October 9th, 2021

Last Reviewed: August 12th, 2022

Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.