Open-label, Single-Center, Phase 1 Study to Estimate the Minimum Effective Dose (MED) of 131I-apamistamab for Non-myeloablative Conditioning in Patients With Severe Sickle Cell Disease
Columbia University
Summary
The purpose of this study is to find the smallest amount of the 131 I-apamistamab needed for preparing patients with severe sickle cell disease (SCD) for a bone marrow transplant. This is the first time 131 I-apamistamab is being used for advanced Sickle Cell Disease (SCD) in the setting of allogeneic stem cell transplant. 131 I-apamistamab is an investigational product. This means that 131 I-apamistamab has not been approved by the Food and Drug Administration (FDA) for medical use in patients. The study treatment that is given before the transplant is called the conditioning regimen. In this study, the investigators are adding a drug called 131 I-apamistamab instead of the conditioning regimen typically given before a stem cell transplant.
Description
The purpose of this study is to research the minimum effective dose (MED) of 131 I-apamistamab conditioning for hematopoietic stem cell transplantation for patients with advanced SCD. 131 Iapamistamab is an investigational product. This means that 131 I-apamistamab has not been approved by the Food and Drug Administration (FDA) for medical use in patients. The study treatment that is given before the transplant is called the conditioning regimen. In this study, investigators are adding 131 I-apamistamab instead of the conditioning regimen typically given before a stem cell transplant. The cu…
Eligibility
- Age range
- 12–50 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Availability of an HLA-matched sibling donor * Patients with sickle cell anemia (Hb SS, Sβ0 thalassemia or severe SC) who are 12 - 50 years of age inclusive AND who have 1 or more of the following: 1. Clinically significant neurologic event (stroke) or any neurological deficit lasting at least 24 hours. Stroke will be defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy. 2. History of two or more episodes of ACS in the 2-year period preceding enrollment d…
Interventions
- Drug131I-apamistmab
131I-apamistamab is a drug construct consisting of the apamistamab monoclonal antibody (mAb) and radioactive isotope iodine 131 (131I). The study drug will be patient-specific and will be manufactured for dosing on a specific date. The antibody dose will be at least 0.5mg/kg, however the final antibody amount may be higher if necessary based on the target radioactivity level. The 131I-apamistamab study drug requires patient details such as height, weight, a calculation to determine weight for use in calculating antibody amount for the dose. 131I-apamistmab will be given via intravenous (IV) infusion.
- DrugSirolimus
Sirolimus is a macrocyclic lactone produced by Streptomyces hygroscopicus. It is an immunosuppressant agent. Sirolimus is to be given orally either as tablet or solution form. Dosage will be adjusted to a therapeutic target of 10-15 ng/mL in first 6 months post-transplant and 5-10 ng/mL after 6 months.
- DrugCampath
Campath is a recombinant DNA-derived humanized monoclonal antibody that is directed against the 21-28 kD cell surface glycoprotein, CD52. CD52 is expressed on the surface of normal and malignant B and T lymphocytes, NK cells, monocytes, macrophages, and tissues of the male reproductive system. Campath will be given via IV at a total dose of 1 mg per kilogram of body weight.
- DrugTotal Body Irradiation
Radiation dose is 3Gy (Gy is a radiation unit of measurement). Radiation source and dose rates will be according to institutional practice. Total Body Irradiation (TBI) may be delivered from either linear accelerator or Cobalt sources.
Location
- Columbia University Irving Medical CenterNew York, New York