Patient case: 72-year-old male with Cholangiocarcinoma. Genetic variant: BRCA2. Other conditions: Diabetes.

Clinical trial: A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in Severe Sickle Cell Disease

Summary: This is a non-randomized, open label, multi-site, single-dose, Phase 1 study in up to 29 adults with severe sickle cell disease (SCD). The study will evaluate the safety and efficacy of the LentiGlobin BB305 Drug Product [consisting of autologous CD34+ hematopoietic stem cells (HSC) transduced with LentiGlobin BB305 lentiviral vector encoding the human beta A-T87Q-globin gene].

Detailed description: Subject participation for this study will be 2 years post-treatment. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 13 years post-transplant.

Eligibility: Inclusion Criteria:
  1. 18 years of age or older.
  2. Diagnosis of sickle cell disease (SCD), with either βS/βS or βS/β0 or βS/β+ genotype.
  3. Have severe SCD. i.e., in the setting of appropriate supportive care measures for SCD (e.g., pain management plan, hydroxyurea), as judged by the Investigator, have experienced one or more of the following events:
  -  Recurrent severe vaso occlusive crises (VOC) (at least 2 episodes per year in the preceding 2 years or in the 2 years prior to initiation of a regular transfusion program).
  -  Acute Chest Syndrome (ACS) (at least 2 total episodes in the prior 2 years, with at least one episode in the past year or in the year prior to the initiation of a regular transfusion program), defined as an acute event with pneumonia-like symptoms and the presence of a new pulmonary infiltrate.
  -  History of an overt stroke, defined as a sudden neurologic change lasting more than 24 hours that is accompanied by cerebral MRI changes.
  -  Echocardiographic evidence of a tricuspid regurgitant jet velocity (TRJV) of > 2.5 m/s.
  4. Medically eligible to undergo hematopoietic stem cell transplant (HSCT).
  5. Karnofsky performance status of ≥ 60.
  6. Subjects should be determined by the investigator to have no physical limitations to undergo general anesthesia and to provide adequate bone marrow harvest from bilateral post-superior iliac sites.
  Exclusion Criteria:
  1. Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
  2. Positive for any active infection.
  3. Any major organ dysfunction (renal, liver, lung and cardiac abnormalities).
  4. Inadequate bone marrow function, as defined by an absolute neutrophil count of < 1000/µL (< 500/µL for subjects on hydroxyurea treatment) or a platelet count < 150,000/µL.
  5. Moyamoya disease on cerebral MRI. Subjects with a history of a revascularization procedure for Moyamoya disease (e.g., encephaloduroarteriosynangiosis (EDAS) procedure) are eligible if the procedure occurred > 1 year prior to study entry.
  6. Contraindication to anesthesia for bone marrow harvesting.
  7. Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
  8. Prior receipt of an allogeneic transplant.
  9. Immediate family member with a known or suspected Familial Cancer Syndrome
  10. Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile subjects.
  11. Participation in another clinical study with an investigational drug within 30 days of Screening.
  12. Prior receipt of gene therapy.

Relevance to patient case: not relevant