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
Patients with Fanconi Anemia
Impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease. Patients with a shortening fraction of < 26% may be enrolled if approved by a cardiologist. In addition, patients with poorly controlled hypertension on multiple anti-hypertensive medications, symptomatic coronary artery disease, or patients on cardiac medications for antiarrhythmic or inotropic effects are excluded
Impaired pulmonary function as evidenced by carbon monoxide diffusing capability test (DLCO) < 35% of predicted or receiving supplemental continuous oxygen. In addition, if patients are unable to perform pulmonary function tests, then O2 saturation < 92% on room air
Impaired renal function as evidenced by estimated creatinine clearance less than 50 ml/min or serum creatinine > 2 x upper normal limit or dialysis-dependent. Serum creatinine value must be within 28 days prior to start of conditioning
Single group
Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
Biological/VaccineGiven IV
Fludarabine
DrugGiven IV
Cyclophosphamide
DrugGiven IV
Lapine T-Lymphocyte Immune Globulin
Biological/VaccineGiven IV
Total-Body Irradiation
RadiationUndergo TBI
Hematopoietic Cell Transplantation
Procedure/SurgeryUndergo hematopoietic cell transplantation
Mycophenolate Mofetil
DrugGiven PO or IV
Sirolimus
DrugGiven PO
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
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.
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.
Transplant related mortality
Overall survival
Rate of acute graft versus host disease (GVHD)
Rate of chronic GVHD
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Fred Hutchinson Cancer Center
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
