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

NCT03670966 | Recruiting Phase 1 DMC FDA Drug

• 5 other identifiers: RG100334910060P30CA015704NCI-2018-01788P01CA078902
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia in Remission; Chronic Myelomonocytic Leukemia; Recurrent Acute Lymphoblastic Leukemia; Refractory Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Myelodysplastic Syndrome With Excess Blasts; Recurrent Acute Myeloid Leukemia; Refractory Acute Lymphoblastic Leukemia; Recurrent Mixed Phenotype Acute Leukemia; Refractory Mixed Phenotype Acute Leukemia; Hematopoietic and Lymphoid Cell Neoplasm

Keywords

Lymphoid Leukemia; Myeloid and Monocytic Leukemia; Other Hematopoietic

Outcome Measures

Primary Outcomes (1)

• Toxicity: Proportion of patients who develop grades III/IV Bearman regimen-related toxicity

  Proportion of patients who develop grades III/IV Bearman regimen-related toxicity.

  Up 100 days after hematopoietic cell transplantation (HCT)

Secondary Outcomes (9)

• Achievement of remission

  Up to 2 years

• Rate of engraftment

  Up to 2 years

• Donor chimerism

  At days 28, 56, 84, 180, and at 1 year

• Non-relapse mortality (NRM)

  Up to 2 years

• Number of patients experiencing Immune reconstitution

  Up to 2 years

Study Arms (1)

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

EXPERIMENTAL

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.

Biological: Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10; Drug: Cyclophosphamide; Radiation: Total-Body Irradiation; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Bone Marrow Transplantation; Drug: Mycophenolate Mofetil; Biological: Recombinant Granulocyte Colony-Stimulating Factor; Drug: Fludarabine Phosphate; Drug: Tacrolimus; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Biospecimen Collection

Interventions

Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10 BIOLOGICAL

Given via infusion

Also known as: At 211 MAb BC8-B10, APAMISTAMAB-B10-ASTATINE AT-211

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, Asta B 518, B-518, WR-138719

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Total-Body Irradiation RADIATION

Undergo TBI

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

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC transplantation

Also known as: PBPC transplantation

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Bone Marrow Transplantation PROCEDURE

Undergo bone marrow transplant

Also known as: Bone Marrow Grafting, BMT

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: 115007-34-6, MMF, Cellcept

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Recombinant Granulocyte Colony-Stimulating Factor BIOLOGICAL

Given IV or SC

Also known as: 143011-72-7, Recombinant Colony-Stimulating Factor 3, rhG-CSF

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara, Fludarabine-5''-Monophosphate, SH T 586

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Tacrolimus DRUG

Given IV or PO

Also known as: Prograf, Protopic, FK 506, FK-506, Tacforius

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (211At-BC8-B10, chemotherapy, TBI, MMF, G-CSF)

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.
• Bilirubin \< 2 times the upper limit of normal.
• 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.

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 \< 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.

Sponsors & Collaborators

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

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

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

Interventions

Cyclophosphamide; Whole-Body Irradiation; Peripheral Blood Stem Cell Transplantation; Bone Marrow Transplantation; Mycophenolic Acid; pegylated granulocyte colony-stimulating factor; fludarabine phosphate; Tacrolimus; Biopsy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical

Study Officials

• Phuong Vo

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Phuong Vo

CONTACT

206-667-2749; ptvo@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: September 12, 2018
• First Posted: September 14, 2018
• Study Start: July 10, 2019
• Primary Completion (Estimated): January 28, 2028
• Study Completion (Estimated): October 20, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)