RECRUITING

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

Conditions

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

Quick Navigation

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 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.

Official Title

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)

Quick Facts

Study Start:2019-07-10

Study Completion:2027-03-20

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03670966

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 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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. * 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.	* 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.

Inclusion Criteria

Exclusion 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.
* 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.
* 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.

* 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.

Contacts and Locations

Study Contact

Phuong Vo

CONTACT

206-667-2749

ptvo@fredhutch.org

Principal Investigator

Phuong Vo

PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Center

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 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 Registration Dates

Study Start Date2019-07-10

Study Completion Date2027-03-20

Study Record Updates

Study Start Date2019-07-10

Study Completion Date2027-03-20

Terms related to this study

Keywords Provided by Researchers

Lymphoid Leukemia
Myeloid and Monocytic Leukemia
Other Hematopoietic

Additional Relevant MeSH Terms

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