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.
OUTLINE: This is a dose-escalation study of ²¹¹At-OKT10-B10. Patients are assigned to 1 of 2 arms. ARM A: Patients with HLA-matched related or unrelated donors receive ²¹¹At-OKT10-B10 intravenously (IV) on day -7 (day -10 to -5) and fludarabine IV over 30 minutes on days -4 to -2. Patients then undergo TBI and allogeneic HCT on day 0. Additionally, patients undergo x-rays on study, and blood sample collection, bone marrow biopsy, and bone marrow aspiration throughout the study. ARM B: Patients with HLA-matched haploidentical donors receive ²¹¹At-OKT10-B10 IV on day -8 (day -14 to -7), fludarabine IV over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on day -6 and -5. Patients then undergo TBI on day -1 and allogeneic HCT on day 0. Additionally, patients undergo x-rays on study, and blood sample collection, bone marrow biopsy, and bone marrow aspiration throughout the study. After completion of study treatment, patients are followed up at 9, 12, 18 and 24 months.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Undergo HCT
Given IV
Given IV
Given IV
Undergo TBI
Undergo blood collection
Undergo bone marrow aspirate
Undergo bone marrow biopsy
Undergo chest x-rays
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
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.
Time frame: Up to 100 days following HCT
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.
Time frame: Between days 70 to 90 post-transplant
Duration of response
Duration of response will be estimated using Kaplan-Meier methodology.
Time frame: From date of response assessment (days +70-90 following allogeneic HCT) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
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.
Time frame: Between days 70 to 90 post-transplant
One-year disease -free survival
Kaplan-Meier methodology will be used to estimate the 1-year disease-free survival.
Time frame: From allogeneic hematopoietic cell transplantation to disease progression, relapse or death, assessed at 1 year
One-year overall survival (OS)
Kaplan-Meier methodology will be used to estimate the 1-year OS.
Time frame: From transplantation to death or last patient contact, assessed at 1 year
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