211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
A Study Evaluating Escalating Doses of 211At-labeled anti-CD45 MAb BC8-B10 (211At-BC8-B10) followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS)
Investigator
Trial Phase
Phase I/II
Study Number
Local Study ID
9595
Trial Contact Phone
800-804-8824 / 206-606-1024
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, or myelodysplastic syndrome. 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.
Trial Eligibility
Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
- Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:
-- * AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)
-- * AML or ALL 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
- 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, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] - Eastern Cooperative Oncology Group (ECOG) = 70
- Patients must be free of uncontrolled infection
- Patients must have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or bone marrow donation, as follows:
-- * Related donor: related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed by high-resolution typing
-- * Unrelated donor:
--- ** Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR
--- ** Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
--- ** 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 transplant (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 mismatch, 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
-- * Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
Other eligibility criteria may apply.
Sexes Eligible for Study: All
- Patients must have advanced AML, ALL or high-risk MDS meeting one of the following descriptions:
-- * AML or ALL beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)
-- * AML or ALL 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
- 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, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] - Eastern Cooperative Oncology Group (ECOG) = 70
- Patients must be free of uncontrolled infection
- Patients must have an HLA-matched related donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) or other donor center criteria for peripheral blood stem cell (PBSC) or bone marrow donation, as follows:
-- * Related donor: related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1; phenotypic identity must be confirmed by high-resolution typing
-- * Unrelated donor:
--- ** Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR
--- ** Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing
--- ** 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 transplant (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 mismatch, 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
-- * Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
Other eligibility criteria may apply.
Trial Exclusions
- 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 - Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) - 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
- 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
Other exclusion criteria may apply.
- Left ventricular ejection fraction - Corrected diffusing capacity of the lungs for carbon monoxide (DLCO) - 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
- 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
Other exclusion criteria may apply.
Trial Keywords
Leukemia, Acute Myeloid (AML); Hematologic Malignancies; Leukemia; Lymphoproliferative Disorders; Myelodysplastic Syndromes (MDS); Leukemia, Myeloid; Leukemia, Lymphoid; Immunoproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Chronic Myelomonocytic (CMML); Preleukemia; Bone Marrow Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Immune System Diseases