A Phase 1 Pilot Study to Evaluate the Safety and Feasibility of Gene Therapy With CSL200 (Autologous Enriched CD34+ Cell Fraction That Contains CD34+ Cells Transduced With Lentiviral Vector Encoding Human γ-GlobinG16D and Short-Hairpin RNA734) in Adult Subjects With Severe Sickle Cell Disease


1 United States site


18 to 45 Years




Phase 1

Study type








About the study

This is a phase 1 pilot study of CSL200 in adult subjects with severe sickle cell disease.
The primary objectives of this study are to evaluate the safety of the following: collection
of CD34+ hematopoietic stem / progenitor cells by apheresis after mobilization with
plerixafor, reduced intensity conditioning with melphalan, and administration of CSL200.

participation requirements

– Diagnosis of sickle cell disease with the homozygous HbS homozygous genotype (HbSS) or
an HbSβ thalassemia variant (ie, HbSβ0 thalassemia or HbSβ+ thalassemia) genotype,
confirmed by hemoglobin studies.

– Fetal hemoglobin (HbF) ≤ 15%.

– Severe sickle cell disease symptomatology, defined as any one or more of the

1. ≥ 2 episodes of acute chest syndrome in the last 2 years.

2. ≥ 3 episodes of severe pain events requiring a visit to a medical facility and
treatment with opioids in the last 2 years.

3. > 2 episodes of recurrent priapism in the last 2 years.

4. Red-cell alloimmunization (> 2 antibodies) during long-term transfusion therapy
(lifetime history).

5. Chronic transfusions for primary or secondary prophylaxis (lifetime history).

6. Trans-thoracic echocardiograph evidence of tricuspid valve regurgitant jet
velocity ≥ 2.7 m/sec (lifetime history).

7. Clinically significant neurologic event (eg, ischemic stroke) or any neurological
deficit lasting > 24 hours.

– Not eligible for human leukocyte antigen (HLA)-matched hematopoietic stem cell
transplantation, defined as follows: no medically eligible, available, and willing
10/10 matched HLA-identical sibling donor, unless subject has declined this treatment
option (as documented in the informed consent form).

– Not eligible for, declined, or, as judged by the investigator, failed therapy with
hydroxyurea and if still on hydroxyurea is able to interrupt hydroxyurea starting at
the beginning of the transfusions, before mobilization and apheresis.

participation restrictions

– Hypoxanthine-guanine phosphoribosyl transferase (HPRT) deficiency.

– Thiopurine S-methyltransferase (TPMT) deficiency.

– Alpha thalassemia.

– Inadequate bone marrow function, defined as at least 1 of the following:

1. Absolute neutrophil count < 1000/µL. 2. Platelet count < 120,000/µL.


  • Duarte, California, United States, City of Hope Medical Center, 91010