211At-BC8-B10 Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory High-Risk Acute Leukemia or Myelodysplastic Syndrome

June 17, 2026 updated by: Fred Hutchinson Cancer Center

A Phase I/II Study Evaluating Escalating Doses of 211At-Labeled Anti-CD45 MAb BC8-B10 (211At-BC8-B10) Followed by Related Haplo-Identical Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Leukemia or Myelodysplastic Syndrome (MDS)

This phase I/II trial studies the side effects and best dose of a radioactive agent linked to an antibody (211At-BC8-B10) followed by donor stem cell transplant in treating patients with high-risk acute leukemia or myelodysplastic syndrome that has come back (recurrent) or isn't responding to treatment (refractory). 211At-BC8-B10 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy and total body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, and tacrolimus after a transplant may stop this from happening.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

OUTLINE: This is a dose-escalation study of astatine At 211 anti-CD45 monoclonal antibody BC8-B10.

PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine intravenously (IV) over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Patients also undergo TBI on day -1.

TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) or bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or PO three times daily (TID) on days 5-35, and tacrolimus IV over 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per physician discretion. Patients also begin granulocyte colony-stimulating factor (G-CSF) IV or subcutaneously (SC) on day 5 to continue until absolute neutrophil count (ANC) > 1000/mm^3 x 3 days.

Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at day 100, and at 6, 9, 12, 18, and 24 months.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch/University of Washington Cancer Consortium
        • Contact:
        • Principal Investigator:
          • Phuong Vo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have AML, ALL, high-risk MDS, or MPAL (also known as biphenotypic) meeting one of the following descriptions:

    • AML, ALL, or MPAL in first remission with evidence of measurable residual disease (MRD) by flow cytometry;
    • AML, ALL, or MPAL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen);
    • AML, ALL, or MPAL representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens);
    • AML evolved from myelodysplastic or myeloproliferative syndromes;
    • MDS expressed as refractory anemia with excess blasts (RAEB)
    • Chronic myelomonocytic leukemia (CMML) by French-American-British (FAB) criteria.
  • Patients not in remission must have CD45-expressing leukemic blasts. Patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up >= 95% of nucleated cells in the marrow).
  • Patients must be >= 18 and =< 75 years of age.
  • Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed).
  • Patients must have an estimated creatinine clearance greater than 50/ml per minute by the following formula (Cockcroft-Gault). Serum creatinine value must be within 28 days prior to registration.
  • Total bilirubin within normal limits
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the upper limit of normal.
  • Eastern Cooperative Oncology Group (ECOG) < 2 or Karnofsky >= 70.
  • Patients must be free of uncontrolled infection.
  • Patients with prior non-myeloablative or reduced-intensity conditioning allogeneic-HCT must have no evidence of ongoing GVHD and be off all immunosuppression for at least 6 weeks at time of enrollment.
  • Patients must have normal elastography.
  • If ferritin is elevated, patient must have less than 7 mg/g liver iron concentration on liver T2 magnetic resonance imaging (MRI).
  • Patients should have an official gastrointestinal (GI) consult prior to the transplant for full evaluation.
  • Patients must have a related donor who is identical for one HLA haplotype and mismatched at the HLA-A, -B or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or DRB1 mismatches.
  • DONOR: Donors must meet HLA matching criteria as well as standard Seattle Cancer Care Alliance (SCCA) criteria for PBSC or bone marrow donation. Preference should be given to donors who are mismatched at the HLA-A, -B and -DRB1 loci.

Exclusion Criteria:

  • Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects.
  • Left ventricular ejection fraction < 45%.
  • Corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen. When pulmonary function tests (PFTs) 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 < 89% 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.
  • Active central nervous system (CNS) leukemia at time of treatment.
  • Patients with prior myeloablative allogeneic-HCT.
  • Women of childbearing potential who are pregnant (beta human chorionic gonadotropin [B-HCG]+) or breast feeding.
  • Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant.
  • Inability to understand or give an informed consent.
  • Allergy to murine-based monoclonal antibodies.
  • Known contraindications to radiotherapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

PREPARATIVE REGIMEN: Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 infusion over 6-8 hours on day -8, fludarabine IV over 30 minutes on days -6 to -2, and cyclophosphamide IV over 1 hour on days -6 and -5. Patients also undergo TBI on day -1.

TRANSPLANT: Patients undergo PBSC or bone marrow transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or PO TID on days 5-35, and tacrolimus IV over 1-2 hours (changed to PO once tolerated) on days 5-180 with taper beginning on day 84 per physician discretion. Patients also begin G-CSF IV or SC on day 5 to continue until ANC > 1000/mm^3 x 3 days.

Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • Asta B 518
  • B-518
  • WR-138719
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • TBI
  • SCT_TBI
  • Whole Body Irradiation
  • Whole-Body Irradiation
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo PBSC transplantation
Other Names:
  • PBPC transplantation
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • SH T 586
  • Fludarabine-5''-Monophosphate
Drug: Tacrolimus
Given IV or PO
Other Names:
  • Prograf
  • FK 506
  • Protopic
  • FK-506
  • Tacforius
Procedure: Bone Marrow Aspiration and Biopsy
Undergo bone marrow biopsy and aspiration
Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
  • 115007-34-6
Biological: Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10
Given via infusion
Other Names:
  • At 211 MAb BC8-B10
  • APAMISTAMAB-B10-ASTATINE AT-211
Procedure: Bone Marrow Transplantation
Undergo bone marrow transplant
Other Names:
  • BMT
  • Bone Marrow Grafting
Biological: Recombinant Granulocyte Colony-Stimulating Factor
Given IV or SC
Other Names:
  • rhG-CSF
  • Recombinant Colony-Stimulating Factor 3
  • 143011-72-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose limiting toxicity (DLT)
Time Frame: Up to 30 days post-transplant, with a review period for occurrence of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) extended to 60 days post-transplant
DLT is defined as a grade III/IV regimen-related toxicity (Bearman scale). The maximum tolerated dose will be defined as the dose of 211^At-BC8-B10 used in combination with the reduced-intensity hematopoietic cell transplantation conditioning regimen that is associated with a grade III/IV regimen-related toxicity or true DLT rate of 25%. The data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels visited. Based on this fitted model, the maximum tolerated dose is estimated to be the dose that is associated with a toxicity rate of 25%.
Up to 30 days post-transplant, with a review period for occurrence of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) extended to 60 days post-transplant

Secondary Outcome Measures

Outcome Measure
Time Frame
Achievement of remission
Time Frame: Up to 2 years
Up to 2 years
Rate of engraftment
Time Frame: Up to 2 years
Up to 2 years
Donor chimerism
Time Frame: At days 28, 56, 84, 180, and at 1 year
At days 28, 56, 84, 180, and at 1 year
Non-relapse mortality (NRM)
Time Frame: Up to 2 years
Up to 2 years
Number of patients experiencing Immune reconstitution
Time Frame: Up to 2 years
Up to 2 years
Number of patients experiencing Number of Grade II-IV acute graft versus host disease (GVHD)
Time Frame: Up to 2 years
Up to 2 years
Number of patients experiencing Moderate/severe chronic GVHD
Time Frame: Up to 2 years
Up to 2 years
Overall survival
Time Frame: Up to 100 days
Up to 100 days
Disease-free survival
Time Frame: Up to day 100
Up to day 100

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Phuong Vo, Fred Hutchinson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2019

Primary Completion (Estimated)

January 28, 2028

Study Completion (Estimated)

October 20, 2029

Study Registration Dates

First Submitted

September 12, 2018

First Submitted That Met QC Criteria

September 12, 2018

First Posted (Actual)

September 14, 2018

Study Record Updates

Last Update Posted (Actual)

June 22, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG1003349
  • P30CA015704 (U.S. NIH Grant/Contract)
  • P01CA078902 (U.S. NIH Grant/Contract)
  • 10060 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
  • NCI-2018-01788 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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