A Phase I Trial Evaluating Escalating Doses of ²¹¹At-Labeled Anti-CD38 Monoclonal Antibody Followed by HLA-Matched or Haploidentical Donor Hematopoietic Cell Transplantation for High-Risk Multiple Myeloma
Fred Hutchinson Cancer Center
Summary
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.
Description
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), fludar…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients with newly diagnosed or relapsed/refractory multiple myeloma * Patients with multiple myeloma must have at least one of the following high-risk features: * 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 primary or secondary plasma cell leukemia * Patients must start ²¹¹At-OKT10-B10 within 40-180 days of autologous stem cell transplant (either as part of…
Interventions
- ProcedureAllogeneic Hematopoietic Stem Cell Transplantation
Undergo HCT
- BiologicalAstatine At 211 Anti-CD38 Monoclonal Antibody OKT10-B10
Given IV
- DrugCyclophosphamide
Given IV
- DrugFludarabine Phosphate
Given IV
- RadiationTotal-Body Irradiation
Undergo TBI
- ProcedureBiospecimen Collection
Undergo blood collection
- ProcedureBone Marrow Aspiration
Location
- Fred Hutch/University of Washington Cancer ConsortiumSeattle, Washington