211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia

NCT03128034 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 9595NCI-2017-00452P01CA078902RG9217014
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of 211\^astatine(At)-BC8-B10 before donor stem cell transplant in treating patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or mixed-phenotype acute leukemia. Radioactive substances, such as astatine-211, linked to monoclonal antibodies, such as BC8, can bind to cancer cells and give off radiation which may help kill cancer cells and have less of an effect on healthy cells before donor stem cell transplant.

Conditions

Myelodysplastic Syndrome With Excess Blasts; Recurrent Acute Myeloid Leukemia; Recurrent Acute Lymphoblastic Leukemia; Recurrent Mixed Phenotype Acute Leukemia; Refractory Acute Myeloid Leukemia; Refractory Mixed Phenotype Acute Leukemia; Mixed Phenotype Acute Leukemia; Refractory Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of grades III/IV Bearman regimen-related toxicity

  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 dose limiting toxicity 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 100 days following hematopoietic cell transplantation

Secondary Outcomes (8)

• Engraftment

  Up to day 100

• Chimerism

  Up to day 84

• Non-relapse mortality

  Up to 2 years

• Acute graft versus host disease

  Up to day 180

• Achievement of remission

  Up to 2 years

Study Arms (1)

Treatment (211^At-BC8-B10, PBSC)

EXPERIMENTAL

Patients receive 211\^At-BC8-B10 IV over 6-8 hours on day -7 and may receive 131\^I-BC8-B10 IV on day -7 and fludarabine phosphate IV over 30 minutes on days -4, -3 and -2. Patients undergo TBI and PBSC transplant on day 0. Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 and then tapered to day 180, or continuing to day 96 and then tapered to day 150. Patients receive mycophenolate mofetil PO or IV (first dose to occur 4-6 hours after PBSC infusion) every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on day 0 and then reduced to every 12 hours on days 30-150 then tapered to day 180 (for patients with unrelated donors). Patients may undergo SPECT, bone marrow aspirate sample and blood sample collection on study.

Drug: Cyclosporine; Drug: Fludarabine Phosphate; Drug: Mycophenolate Mofetil; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Pretargeted Radioimmunotherapy; Radiation: Total-Body Irradiation; Procedure: Biospecimen Collection; Procedure: Single Photon Emission Computed Tomography

Interventions

Pretargeted Radioimmunotherapy RADIATION

Given 211\^At-BC8-B10 IV

Treatment (211^At-BC8-B10, PBSC)

Biospecimen Collection PROCEDURE

Undergo blood and bone marrow aspirate sample collection

Also known as: Biological Sample Collection

Treatment (211^At-BC8-B10, PBSC)

Mycophenolate Mofetil DRUG

Given PO or IV

Also known as: Cellcept, MMF

Treatment (211^At-BC8-B10, PBSC)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (211^At-BC8-B10, PBSC)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation, TBI, Whole Body Irradiation, SCT_TBI

Treatment (211^At-BC8-B10, PBSC)

Single Photon Emission Computed Tomography PROCEDURE

Undergo SPECT

Also known as: SPECT, SPECT SCAN, Medical Imaging

Treatment (211^At-BC8-B10, PBSC)

Cyclosporine DRUG

Given PO or IV

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (211^At-BC8-B10, PBSC)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (211^At-BC8-B10, PBSC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients must have normal hepatic function (bilirubin within normal limits, aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\] \< 2 times the upper limit of normal) within 2 months prior to the astatine-211 infusion date (with the exception of patients that are known to have Gilbert's disease, for whom total bilirubin is allowed up to 3 x upper limit of normal \[ULN\])
• 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-hematopoietic cell transplant (HCT) must have no evidence of ongoing GVHD and be off GVHD treatment immunosuppression for at least 6 weeks at time of enrollment

You may not qualify if:

• 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 \< 35%
• Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) \< 35% or receiving supplemental continuous oxygen; when pulmonary function test (PFT)s 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 positive \[beta-HCG+\] 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

Related Publications (1)

• Li Y, Hamlin DK, Chyan MK, Wong R, Dorman EF, Emery RC, Woodle DR, Manger RL, Nartea M, Kenoyer AL, Orozco JJ, Green DJ, Press OW, Storb R, Sandmaier BM, Wilbur DS. cGMP production of astatine-211-labeled anti-CD45 antibodies for use in allogeneic hematopoietic cell transplantation for treatment of advanced hematopoietic malignancies. PLoS One. 2018 Oct 18;13(10):e0205135. doi: 10.1371/journal.pone.0205135. eCollection 2018.

  PMID: 30335787 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts; Leukemia, Biphenotypic, Acute

Interventions

Cyclosporine; Cyclosporins; fludarabine phosphate; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation; X-Rays

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Brenda M. Sandmaier

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brenda M. Sandmaier

CONTACT

206-667-4961; bsandmai@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 25, 2017
• Study Start: October 24, 2017
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): March 31, 2029
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

US (1)