Total Body Irradiation and Astatine-211-Labeled BC8-B10 Monoclonal Antibody for the Treatment of Nonmalignant Diseases

NCT04083183 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: RG1005632NCI-2019-057279524P01HL122173-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose of total body irradiation with astatine-211 BC8-B10 monoclonal antibody for the treatment of patients with nonmalignant diseases undergoing hematopoietic cell transplant. Radiation therapy uses high energy gamma rays to kill cancer cells and shrink tumors. Astatine-211-labeled BC8-B10 monoclonal antibody is a monoclonal antibody, called anti-CD45 monoclonal antibody BC8-B10, linked to a radioactive/toxic agent called astatine 211. Anti-CD45 monoclonal antibody BC8-B10 is attached to CD45 antigen positive cancer cells in a targeted way and delivers astatine 211 to kill them. Giving astatine-211 BC8-B10 monoclonal antibody and total-body irradiation before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells.

Conditions

Non-Malignant Neoplasm

Outcome Measures

Primary Outcomes (2)

• Graft rejection (arm A)

  Defined as establishment of \< 5% donor chimerism of CD3+ T cells and \<5% donor chimerism of CD33+ myeloid cells at day 80-100 after hematopoietic cell transplant (HCT) following an human leukocyte antigen (HLA)-matched related or unrelated graft or an unrelated graft with a single HLA-class 1 allele mismatch or DQB1 antigen or allele mismatch.

  Up to 5 years post-transplant

• Graft rejection (arm B)

  Defined as establishment of \< 5% donor chimerism of CD3+ T cells and \< 5% donor chimerism of CD33+ myeloid cells at day 80-100 after HCT following an HLA-haploidentical related donor or an unrelated donor mismatched for a single HLA-class 1 antigen or a single HLA-DRB1 allele.

  Up to 5 years post-transplant

Secondary Outcomes (5)

• Transplant related mortality

  At day 100 post-transplant

• Overall survival

  At 1 year post-transplant

• Rate of acute graft versus host disease (GVHD)

  At day 100 post-transplant

• Rate of chronic GVHD

  At 1 year post-transplant

• Donor chimerism

  At day 28, day 84, and 1 year post-transplant

Study Arms (1)

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

EXPERIMENTAL

Patients receive astatine At 211 anti-CD45 monoclonal antibody BC8-B10 IV on any day between days -10 and -7, fludarabine IV on days -6 to -2, cyclophosphamide IV over 1 hour on days -6 to -5 and 3 to 4, and thymoglobulin IV over 4-6 hours on days -4 to -2. Patients undergo TBI on day -1 and hematopoietic cell transplant on day 0. Beginning day 5, patients also receive mycophenolate mofetil PO or IV thrice daily every 8 hours up to day 35 if no GVHD present and sirolimus PO daily until day 365. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.

Biological: Astatine At 211 Anti-CD45 Monoclonal Antibody BC8-B10; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Lapine T-Lymphocyte Immune Globulin; Radiation: Total-Body Irradiation; Procedure: Hematopoietic Cell Transplantation; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Procedure: Bone Marrow Aspiration; Procedure: Biospecimen Collection

Interventions

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

Given IV

Also known as: Astatine 211-Labeled Anti-CD45 Monoclonal Antibody BC8-B10, Astatine At 211 MAb BC8-B10, At 211 Anti-CD45 Monoclonal Antibody BC8-B10, At 211 MAb BC8-B10, APAMISTAMAB-B10-ASTATINE AT-211

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Fludarabine DRUG

Given IV

Also known as: 2-Fluorovidarabine, 21679-14-1, 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine, 9-Beta-D-arabinofuranosyl-2-fluoroadenine, Fluradosa, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 21679-14-1

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Cyclophosphamide DRUG

Given IV

Also known as: Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclostin, Cyclostine, Cytoxan, WR-138719

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Lapine T-Lymphocyte Immune Globulin BIOLOGICAL

Given IV

Also known as: Anti-thymocyte Globulin Rabbit, Grafalon, Rabbit Anti-Human Thymocyte Globulin (RATG), Rabbit Anti-Thymocyte Globulin, Rabbit Antithymocyte Globulin, Rabbit ATG, rATG, Thymoglobulin

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, TOTAL BODY IRRADIATION, Whole Body Irradiation, Whole-Body Irradiation, SCT_TBI

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Hematopoietic Cell Transplantation PROCEDURE

Undergo hematopoietic cell transplantation

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Mycophenolate Mofetil DRUG

Given PO or IV

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

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Sirolimus DRUG

Given PO

Also known as: RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Treatment (astatine 211,fludarabine,cyclophosphamide,TBI,HCT)

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age \>= 18 years and \< 50 years
• Nonmalignant disease treatable by allogeneic hematopoietic cell transplantation (HCT). Patients with a nonmalignant disease that is not clearly defined must be approved by the principal investigator (PI)
• Karnofsky score \>= 70
• 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
• HLA matched related donor that is genotypically or phenotypically identical for HLA-A, -B, -C, -DRB1, -DQB1. Phenotypic identity must be confirmed by high-resolution typing. Sibling donors are preferred over other relationships
• Unrelated donor.
• Matched for HLA-A, -B, -C, -DRB1, and DQB1 by high-resolution typing; OR
• Mismatched for a single HLA-class 1 allele or HLA-DQB1 antigen or allele by high-resolution typing.
• Note: A donor homozygous for one allele only at HLA-A, B, C, DRB1, or DQB1 is allowed (1 antigen mismatch for graft versus host disease \[GVHD\], 0 antigen mismatch for graft-rejection). In the case of a recipient who is homozygous at one locus, the mismatch is not allowed to be at that locus (0 antigen mismatch for GVHD, 1 antigen mismatch for graft-rejection)
• HLA haploidentical donor. There must be one shared HLA-haplotype based on inheritance. The noninherited haplotype is allowed to be mismatched at any or all of these loci: HLA-A, B, C, DRB1 or DQB1.
• Donor selection guideline recommendations: in the case where there are multiple donor options, donors should be selected based on the following priority numbered below:
• Related donor genotypically HLA-matched
• Related donor phenotypically HLA-matched

You may not qualify if:

• Patients with Fanconi Anemia
• Impaired cardiac function as evidenced by ejection fraction \< 35% (or, if unable to obtain ejection fraction, shortening fraction of \< 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease. Patients with a shortening fraction of \< 26% may be enrolled if approved by a cardiologist. In addition, patients with poorly controlled hypertension on multiple anti-hypertensive medications, symptomatic coronary artery disease, or patients on cardiac medications for antiarrhythmic or inotropic effects are excluded
• Impaired pulmonary function as evidenced by carbon monoxide diffusing capability test (DLCO) \< 35% of predicted or receiving supplemental continuous oxygen. In addition, if patients are unable to perform pulmonary function tests, then O2 saturation \< 92% on room air
• Impaired renal function as evidenced by estimated creatinine clearance less than 50 ml/min or serum creatinine \> 2 x upper normal limit or dialysis-dependent. Serum creatinine value must be within 28 days prior to start of conditioning
• \* The creatinine clearance may be estimated by the Cockcroft-Gault formula
• Impaired liver function as evidenced by abnormal hepatic function within 2 months prior to the astatine-211 infusion date defined as a total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) \> 2 times the upper limit of normal (with the exception of elevated total bilirubin level, predominantly indirect bilirubin, in patients with hemoglobinopathy due to acute and/or chronic hemolysis). In addition, patients with the following liver abnormalities are excluded: 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
• An uncontrolled infection requiring deferral of conditioning as recommended by an infectious disease specialist. A viral upper respiratory tract infection does not constitute an uncontrolled infection in this context
• Patients who are known to be positive for HIV (human immunodeficiency virus)
• Women of childbearing potential who are pregnant or breast-feeding
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
• Allergy to murine-based monoclonal antibodies
• Known contraindication to radiotherapy

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Antilymphocyte Serum; thymoglobulin; Whole-Body Irradiation; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Mycophenolic Acid; Sirolimus

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Radiotherapy; Therapeutics; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Phuong Vo

  Fred Hutch/University of Washington Cancer Consortium

  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 6, 2019
• First Posted: September 10, 2019
• Study Start: June 16, 2020
• Primary Completion (Estimated): January 9, 2028
• Study Completion (Estimated): January 9, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)