Targeted Astatine-211-Labeled BC8-B10 Monoclonal Antibody as Reduced Intensity Conditioning for Nonmalignant Diseases
This phase I/II trial studies the best dose of total body irradiation with astatine-211 BC8-B10 monoclonal antibody for the treatment of patients with nonmalignant diseases undergoing hematopoietic cell transplant. Radiation therapy uses high energy gamma rays to kill cancer cells and shrink tumors. Astatine-211-labeled BC8-B10 monoclonal antibody is a monoclonal antibody, called anti-CD45 monoclonal antibody BC8-B10, linked to a radioactive/toxic agent called astatine 211. Anti-CD45 monoclonal antibody BC8-B10 is attached to CD45 antigen positive cancer cells in a targeted way and delivers astatine 211 to kill them. Giving astatine-211 BC8-B10 monoclonal antibody and total-body irradiation before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells.
• Age \>= 18 years and \< 50 years
• Nonmalignant disease treatable by allogeneic hematopoietic cell transplantation (HCT). Patients with a nonmalignant disease that is not clearly defined must be approved by the principal investigator (PI)
• Karnofsky score \>= 70
• Patients must have normal elastography
• If ferritin is elevated, patient must have less than 7 mg/g liver iron concentration on liver T2 magnetic resonance imaging (MRI)
• Patients should have an official gastrointestinal (GI) consult prior to the transplant for full evaluation
• DONOR INCLUSION
• HLA matched related donor that is genotypically or phenotypically identical for HLA-A, -B, -C, -DRB1, -DQB1. Phenotypic identity must be confirmed by high-resolution typing. Sibling donors are preferred over other relationships
• Unrelated donor.
‣ Matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing; OR
⁃ Mismatched for a single HLA-class 1 allele or HLA-DQB1 antigen or allele by high-resolution typing.
∙ Note: A donor homozygous for one allele only at HLA-A, B, C, DRB1, or DQB1 is allowed (1 antigen mismatch for graft versus host disease \[GVHD\], 0 antigen mismatch for graft-rejection). In the case of a recipient who is homozygous at one locus, the mismatch is not allowed to be at that locus (0 antigen mismatch for GVHD, 1 antigen mismatch for graft-rejection)
• HLA haploidentical donor. There must be one shared HLA-haplotype based on inheritance. The noninherited haplotype is allowed to be mismatched at any or all of these loci: HLA-A, B, C, DRB1 or DQB1.
• Donor selection guideline recommendations: in the case where there are multiple donor options, donors should be selected based on the following priority numbered below:
‣ Related donor genotypically HLA-matched
⁃ Related donor phenotypically HLA-matched
⁃ Unrelated donor HLA-matched
⁃ Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C). For example, HLA-A02:01 versus HLA-A 02:02
⁃ Unrelated donor with single allele level mismatch at DQB1
⁃ HLA-haploidentical donor Note: We require that the donor testing be performed by a United States Clinical Laboratory Improvement Amendment (CLIA) approved laboratory. In the very rare case where the donor testing is not able to be performed in a CLIA approved laboratory, or there is confirmatory testing that needs to be performed, or for any donor identified from Europe and at risk for Creutzfeldt-Jakob Disease (CJD), we note this on the donor screening form and require that the unrelated donor medical director or the attending physician approves the use of the donor HPC-A product under urgent medical need