Hematopoietic Cell Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Radiolabeled DOTA-Biotin Pretargeted by BC8 Antibody-Streptavidin Conjugate
I. To estimate the maximum tolerated dose (MTD) of radiation delivered via PRIT using BC8-SA
(BC8 antibody-streptavidin conjugate) when combined with fludarabine (FLU), 2 Gy total body
irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and allogeneic
hematopoietic cell transplant (HCT) in patients who have advanced acute myeloid leukemia
(AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS).
I. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting
from this combined preparative regimen.
II. To estimate rates of disease relapse, acute graft-versus-host disease (GvHD), and
day-100 disease-free survival in patients receiving PRIT using BC8-SA combined with FLU, 2
Gy TBI, CSP, MMF, and allogeneic HCT.
III. To assess biodistribution, serum half-life, urinary excretion, tissue localization, and
clearance of BC8-SA conjugate and DOTA-biotin.
IV. To assess the feasibility of yttrium y 90 (90Y)-DOTA-biotin to bind to BC8-SA conjugate
localized to hematolymphoid tissues.
Patients undergo pretargeted radioimmunotherapy comprising a test dose of BC8-SA conjugate
intravenously (IV) on day -22 and indium In 111(111In)-DOTA-biotin IV on day -20, followed
by a therapy dose of BC8-SA conjugate IV on day -14 and 90Y-DOTA-biotin IV on day -12.
Patients receive fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and then
peripheral blood stem cell transplantation on day 0. Patients with matched related donors
receive cyclosporine IV on days -3 to 56 and taper to day 180 and mycophenolate mofetil
orally (PO) twice daily (BID) on days 0-27. Patients with matched unrelated donors receive
cyclosporine IV on days -3 to 100 and taper to day 180 and mycophenolate mofetil PO thrice
daily (TID) on days 0- 40 and taper to day 96.
After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24
months, and then periodically thereafter.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of dose-limiting toxicities (DLT) (Grade III/IV Bearman) to determine MTD of radiation delivered to normal organ by pretargeted 90Y-DOTA-biotin
Conducted by the "two-stage" approach introduced by Storer. The MTD will be defined as the dose of 90Y-DOTA-biotin used in combination with the non-myeloablative HCT conditioning regimen that is associated with a Grade III/IV regimen related toxicity (RRT) or true DLT rate of 25%.
Within 100 days post-transplant
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|