This phase I trial investigates the side effects and best dose of ²¹¹At-OKT10-B10 when given together with fludarabine, alone or in combination with cyclophosphamide and low-dose total-body irradiation (TBI) before donor stem cell transplant in treating patients with high-risk multiple myeloma that is newly diagnosed, has come back (recurrent), or does not respond to treatment (refractory). ²¹¹At-OKT10-B10 is a monoclonal antibody, called OKT10-B10, linked to a radioactive agent called ²¹¹At. OKT10-B10 attaches to CD38 positive cancer cells in a targeted way and delivers ²¹¹At to kill them. Chemotherapy drugs, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy such as TBI uses high energy x-rays to kill cancer cells and shrink tumors. Giving ²¹¹At-OKT10-B10 together with chemotherapy and TBI before a donor stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.
Patients with newly diagnosed or relapsed/refractory multiple myeloma
t(4;14), t(14;16), t(14;20) or deletion 17p, gain in chromosome 1q (> 3 copies of CKS1b) by fluorescence in situ hybridization (FISH); hypodiploidy; complex karyotype
Revised International Staging System III
Plasmablastic morphology
History of central nervous system involvement by multiple myeloma
Presence of circulating plasma cells in the peripheral blood of 5% or more by flow cytometry or morphology
Prior radioimmunotherapy or radiation of > 20 Gy to pelvis or at maximally tolerated levels to any critical normal organ
Prior allogeneic HCT
Parallel
Allogeneic Hematopoietic Stem Cell Transplantation
Procedure/SurgeryUndergo HCT
Astatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
Biological/VaccineGiven IV
Cyclophosphamide
DrugGiven IV
Fludarabine Phosphate
DrugGiven IV
Total-Body Irradiation
RadiationUndergo TBI
Biospecimen Collection
Procedure/SurgeryUndergo blood collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspirate
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
X-Ray Imaging
Procedure/SurgeryUndergo chest x-rays
Maximum tolerated dose (MTD) of radiation delivered via ²¹¹At-OKT10-B10
MTD is defined as the dose of ²¹¹At-OKT10-B10 associated with a true dose limiting toxicity (DLT) rate of 25%, where DLT is defined as grade III/IV regimen-related toxicity according to the Bearman Scale.
Disease response
Definition of disease status will be performed using the established International Myeloma Working Group (IMWG) response criteria for stringent complete response, complete response, partial response (PR) and no response. Relapse is defined per IMWG criteria. The response rates (PR or better) will be estimated along with the exact 95% confidence interval.
Duration of response
Duration of response will be estimated using Kaplan-Meier methodology.
Minimal residual disease (MRD)
MRD will be assessed in the comprehensive response evaluation/restaging. The proportion who achieve MRD will be estimated along with an exact 95% confidence interval.
One-year disease -free survival
Kaplan-Meier methodology will be used to estimate the 1-year disease-free survival.
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Fred Hutchinson Cancer Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
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