RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Targeted Astatine-211-Labeled BC8-B10 Monoclonal Antibody as Reduced Intensity Conditioning for Nonmalignant Diseases

Quick Facts

Study Start:2020-06-16

Study Completion:2028-01-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04083183

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.

Ages Eligible for Study:18 Years to 49 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * DONOR INCLUSION * 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. * 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 * Unrelated donor HLA-matched * Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C). For example, HLA-A02:01 versus HLA-A 02:02 * Unrelated donor with single allele level mismatch at DQB1 * HLA-haploidentical donor Note: We require that the donor testing be performed by a United States Clinical Laboratory Improvement Amendment (CLIA) approved laboratory. In the very rare case where the donor testing is not able to be performed in a CLIA approved laboratory, or there is confirmatory testing that needs to be performed, or for any donor identified from Europe and at risk for Creutzfeldt-Jakob Disease (CJD), we note this on the donor screening form and require that the unrelated donor medical director or the attending physician approves the use of the donor HPC-A product under urgent medical need	* 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 * 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 * DONOR EXCLUSION * Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment. The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplantation (HCT). If the PRA shows \> 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained. The donor should be excluded if any of the cytotoxic cross match assays are positive. For those patients with an HLA class I allele or class II allele or antigen mismatch or haploidentical donors, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results. A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion

Inclusion Criteria

Exclusion Criteria

* 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
* DONOR INCLUSION
* 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.
* 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
* Unrelated donor HLA-matched
* Unrelated donor with single allele level mismatch at class 1 (HLA-A, -B, or -C). For example, HLA-A02:01 versus HLA-A 02:02
* Unrelated donor with single allele level mismatch at DQB1
* HLA-haploidentical donor Note: We require that the donor testing be performed by a United States Clinical Laboratory Improvement Amendment (CLIA) approved laboratory. In the very rare case where the donor testing is not able to be performed in a CLIA approved laboratory, or there is confirmatory testing that needs to be performed, or for any donor identified from Europe and at risk for Creutzfeldt-Jakob Disease (CJD), we note this on the donor screening form and require that the unrelated donor medical director or the attending physician approves the use of the donor HPC-A product under urgent medical need

* 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
* 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
* DONOR EXCLUSION
* Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment. The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplantation (HCT). If the PRA shows \> 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained. The donor should be excluded if any of the cytotoxic cross match assays are positive. For those patients with an HLA class I allele or class II allele or antigen mismatch or haploidentical donors, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results. A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion

Contacts and Locations

Study Contact

Phuong Vo

CONTACT

206-667-2749

ptvo@fredhutch.org

Principal Investigator

Phuong Vo

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

Phuong Vo, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

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 Registration Dates

Study Start Date2020-06-16

Study Completion Date2028-01-09

Study Record Updates

Study Start Date2020-06-16

Study Completion Date2028-01-09

Terms related to this study

Additional Relevant MeSH Terms

Non-Malignant Neoplasm