²¹¹At-OKT10-B10 and Fludarabine Alone or in Combination With Cyclophosphamide and Low-Dose TBI Before Donor Stem Cell Transplant for the Treatment of Newly Diagnosed, Recurrent, or Refractory High-Risk Multiple Myeloma
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
4 other identifiers
interventional
30
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 multiple-myeloma
Started Jun 2026
Shorter than P25 for phase_1 multiple-myeloma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 23, 2020
CompletedFirst Posted
Study publicly available on registry
October 8, 2020
CompletedStudy Start
First participant enrolled
June 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
Study Completion
Last participant's last visit for all outcomes
December 31, 2028
March 13, 2026
June 1, 2025
1.6 years
September 23, 2020
March 11, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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.
Up to 100 days following HCT
Secondary Outcomes (5)
Disease response
Between days 70 to 90 post-transplant
Duration of response
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)
Between days 70 to 90 post-transplant
One-year disease -free survival
From allogeneic hematopoietic cell transplantation to disease progression, relapse or death, assessed at 1 year
One-year overall survival (OS)
From transplantation to death or last patient contact, assessed at 1 year
Study Arms (2)
Arm A (²¹¹At-OKT10-B10, fludarabine, TBI, HCT)
EXPERIMENTALPatients with HLA-matched related or unrelated donors receive ²¹¹At-OKT10-B10 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 (²¹¹At-OKT10-B10, chemotherapy, TBI, HCT)
EXPERIMENTALPatients 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.
Interventions
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
Eligibility Criteria
You may qualify if:
- 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 their induction, or as salvage)
- Patients must have an estimated creatinine clearance greater than 50/ml per minute measured by 24-hour urine collection
- Total bilirubin \< 2 times the upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2 times the upper limit of normal)
- Patients must have an Eastern Cooperative Oncology Group (ECOG) =\< 2 or Karnofsky \>= 70
- Patients must have CD38+ myeloma cells as demonstrated by either flow cytometry or immunohistochemistry in most recent bone marrow that had evidence of clonal plasma cells
- For patients of childbearing potential, must have a negative urinary pregnancy test on the day of and prior to infusion of ²¹¹At-OKT10-B10
- Ability to provide informed consent
- Patients must have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Fred Hutchinson Cancer Center and/or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or bone marrow donation, as follows:
- +6 more criteria
You may not qualify if:
- 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
- More than two prior autologous HCTs
- Patients with plasmacytomas \> 1 cm in bone marrow or any extramedullary plasmacytoma. Previously fludeoxyglucose F-18 (FDG) avid mass lesions by positron emission tomography (PET) that are no longer hypermetabolic following the most recent cycle of therapy are exempt, as are plasmacytomas irradiated with curative intent (\>= 35 Gy)
- Patients with symptomatic coronary artery disease defined as having angina or anginal equivalent, and/or arrhythmias requiring anti-arrhythmics for rhythm control
- History of reactive airway disease and clinically significant asthma requiring ongoing treatment
- Patients with the following organ dysfunction:
- Left ventricular ejection fraction \< 40% in patients with HLA-matched or unrelated donor or \< 45% in patients with an HLA-haploidentical donor
- New York Heart Association (NYHA) class \> 1 heart failure
- Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) \< 50% or receiving supplemental continuous oxygen. When pulmonary function tests cannot be obtained, the 6-minute walk test (6MWT, also known as exercise oximetry) will be used: Any patient with oxygen saturation on room air of \< 90% during a 6MWT will be excluded
- Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease
- Patients who are known to be seropositive for human immunodeficiency virus (HIV)
- Perceived inability to tolerate diagnostic or therapeutic procedures
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Phuong Vo
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2020
First Posted
October 8, 2020
Study Start (Estimated)
June 1, 2026
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
March 13, 2026
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share