Targeted Astatine-211-Labeled BC8-B10 Monoclonal Antibody as Reduced Intensity Conditioning for Nonmalignant Diseases
Summary
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.
Detailed description
OUTLINE: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 intravenously (IV) on any day between days -10 and -7, fludarabine IV on days -6 to -2, cyclophosphamide IV over 1 hour on days -6 to -5 and 3 to 4, and thymoglobulin IV over 4-6 hours on days -4 to -2. Patients undergo TBI on day -1 and hematopoietic cell transplant on day 0. Beginning day 5, patients also receive mycophenolate mofetil orally (PO) or IV thrice daily every 8 hours up to day 35 if no GVHD present and sirolimus PO daily until day 365. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study. After completion of study treatment, patients are followed up at 1 and 2 years and then periodically for up to 5 years. Note: National Heart, Lung, and Blood Institute (NHLBI) funding for this study ended in 2022.
Arms & interventions
- BiologicalAstatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
Given IV
- DrugFludarabine
Given IV
- DrugCyclophosphamide
Given IV
- BiologicalLapine T-Lymphocyte Immune Globulin
Given IV
- RadiationTotal-Body Irradiation
Undergo TBI
- ProcedureHematopoietic Cell Transplantation
Undergo hematopoietic cell transplantation
- DrugMycophenolate Mofetil
Given PO or IV
- DrugSirolimus
Given PO
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBiospecimen Collection
Undergo blood sample collection
Outcome measures
Primary
Graft rejection (arm A)
Defined as establishment of \< 5% donor chimerism of CD3+ T cells and \<5% donor chimerism of CD33+ myeloid cells at day 80-100 after hematopoietic cell transplant (HCT) following an human leukocyte antigen (HLA)-matched related or unrelated graft or an unrelated graft with a single HLA-class 1 allele mismatch or DQB1 antigen or allele mismatch.
Time frame: Up to 5 years post-transplant
Graft rejection (arm B)
Defined as establishment of \< 5% donor chimerism of CD3+ T cells and \< 5% donor chimerism of CD33+ myeloid cells at day 80-100 after HCT following an HLA-haploidentical related donor or an unrelated donor mismatched for a single HLA-class 1 antigen or a single HLA-DRB1 allele.
Time frame: Up to 5 years post-transplant
Secondary
Transplant related mortality
Time frame: At day 100 post-transplant
Overall survival
Time frame: At 1 year post-transplant
Rate of acute graft versus host disease (GVHD)
Time frame: At day 100 post-transplant
Rate of chronic GVHD
Time frame: At 1 year post-transplant
Donor chimerism
Time frame: At day 28, day 84, and 1 year post-transplant
Eligibility criteria
Study locations (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109