NCT01300572 · REGISTRY CONDITION SEARCH

Yttrium-90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk AML, ALL, or MDS

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2019-12-10

This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90 anti-cluster of differentiation 45 (CD45) monoclonal antibody BC8 (90Y-BC8) followed by donor stem cell transplant in treating patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) that is likely to come back or spread. Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body irradiation (TBI) before a donor peripheral blood stem cell (PBSC) or bone marrow transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies, such as 90Y-BC8, can find cancer cells and carry cancer-killing substances to them without harming normal 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 make an immune response against the body's normal cells. Giving FLU, 90Y-BC8, and TBI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

The MTD of Radiation Delivered Via 90Y-DOTA-BC8 When Combined With FLU and 2 Gy TBI as a Preparative Regimen for Patients Aged ≥ 18 With Advanced AML, ALL, and High-risk MDS.

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outcome · POSTED

Achievement of Remission

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outcome · POSTED

Disease-free Survival

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outcome · POSTED

Duration of Remission

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outcome · POSTED

Estimation of Absorbed Radiation Doses to Normal Organs, Marrow and Tumor

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outcome · POSTED

Overall Survival

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outcome · POSTED

Rates of Acute GvHD

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outcome · POSTED

Rates of Donor Chimerism

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outcome · POSTED

Rates of Engraftment

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outcome · POSTED

Rates of Non-relapse Mortality

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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; or * MDS expressed as refractory anemia with excess blasts (RAEB) or 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 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 (serum creatinine value must be within 28 days prior to registration) * Bilirubin \< 2 times the upper limit of normal * Aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 2 times the upper limit of normal * Eastern Cooperative Oncology Group (ECOG) =\< 2 or Karnofsky \>= 70 * Patients must have an expected survival of \> 60 days and must be free of active infection * Patients must have an human leukocyte antigen (HLA)-identical sibling 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 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 * Doors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; 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 and 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 * DONOR: Donors must meet HLA matching criteria and standard SCCA and/or National Marrow Donor Program (NMDP) or other donor center criteria for PBSC or bone marrow donation Exclusion Criteria: * Circulating human anti-mouse antibody (HAMA) * Prior radiation to maximally tolerated levels to any critical normal organ, or \> 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis) * 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 \< 35% * Corrected diffusion lung capacity of carbon monoxide (DLCO) \< 35% or receiving supplemental continuous oxygen * 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 \[HCG+\]) 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
PREPARATIVE REGIMEN: Patients receive 90Y-BC8 via central line on approximately day -12, fludarabine phosphate IV over 30 minutes on days -4 to -2, and 2 Gy TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSC or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients receive mycophenolate mofetil PO or IV every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on days 0-40 with taper to day 96 (for patients with unrelated donors). Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 (for patients with related donors) or 100 (for patients with unrelated donors) with taper to day 180.
intervention Names
Procedure: Allogeneic Bone Marrow Transplantation
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Cyclosporine
Drug: Fludarabine Phosphate
Biological: Indium In 111 Anti-CD45 Monoclonal Antibody BC8
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Procedure: Peripheral Blood Stem Cell Transplantation
Other: Pharmacological Study
Radiation: Total-Body Irradiation
Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
label
Y-90-BC8 & Allogeneic Transplant
type
EXPERIMENTAL

interventions

arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Undergo allogeneic bone marrow transplant
name
Allogeneic Bone Marrow Transplantation
other Names
Allo BMT
Allogeneic BMT
type
PROCEDURE
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Undergo allogeneic PBSC or bone marrow transplant
name
Allogeneic Hematopoietic Stem Cell Transplantation
other Names
allogeneic stem cell transplantation
HSC
HSCT
type
PROCEDURE
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Given PO or IV
name
Cyclosporine
other Names
27-400
Ciclosporin
CsA
Cyclosporin
Cyclosporin A
Gengraf
Neoral
OL 27-400
Sandimmun
Sandimmune
SangCya
type
DRUG
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Given IV
name
Fludarabine Phosphate
other Names
2-F-ara-AMP
9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
Beneflur
Fludara
SH T 586
type
DRUG
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Given IV (dosimetric dose)
name
Indium In 111 Anti-CD45 Monoclonal Antibody BC8
other Names
In 111 MOAB BC8
In 111 Monoclonal Antibody BC8
Indium In 111 Monoclonal Antibody BC8
monoclonal antibody BC8, indium In 111
type
BIOLOGICAL
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Given PO or IV
name
Mycophenolate Mofetil
other Names
Cellcept
MMF
type
DRUG
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Undergo allogeneic PBSC transplant
name
Peripheral Blood Stem Cell Transplantation
other Names
PBPC transplantation
Peripheral Blood Progenitor Cell Transplantation
Peripheral Stem Cell Support
Peripheral Stem Cell Transplantation
type
PROCEDURE
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Correlative studies
name
Pharmacological Study
type
OTHER
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Undergo TBI
name
Total-Body Irradiation
other Names
TOTAL BODY IRRADIATION
Whole-Body Irradiation
type
RADIATION
arm Group Labels
Y-90-BC8 & Allogeneic Transplant
description
Given via central line (therapeutic dose)
name
Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
other Names
90Y Anti-CD45 MoAb BC8
type
RADIATION

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 16
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
The MTD will be defined as the dose that is associated with a true DLT rate of 25%. The highest dose achieved was 28 Gy but none of the patients experienced a DLT. Thus, the MTD was not reached.
measure
The MTD of Radiation Delivered Via 90Y-DOTA-BC8 When Combined With FLU and 2 Gy TBI as a Preparative Regimen for Patients Aged ≥ 18 With Advanced AML, ALL, and High-risk MDS.
time Frame
Within the first 30 days following transplant

secondary Outcomes

description
Number of participants who are in complete remission (CR) 4 weeks after transplant. CR is defined as complete resolution of all signs of myelodysplasia or leukemia for at least 4 weeks with all of the following: 1. Normal bone marrow with blasts \<5% with normal cellularity, normal megakaryopoiesis, \> 15% erythropoiesis and \> 25% granulocytopoiesis 2. Normalization of blood counts (no blasts, platelets \> 100000/mm3, granulocytes \>1500/mm3) 3. No extramedullary disease.
measure
Achievement of Remission
time Frame
4 weeks after transplant
description
Number of study participants who are alive and remains in complete remission after transplant.
measure
Disease-free Survival
time Frame
100 days after transplant
description
Median time to relapse after achieving complete remission (CR). CR is defined as complete resolution of all signs of myelodysplasia or leukemia for at least 4 weeks with all of the following: 1. Normal bone marrow with blasts \<5% with normal cellularity, normal megakaryopoiesis, \> 15% erythropoiesis and \> 25% granulocytopoiesis 2. Normalization of blood counts (no blasts, platelets \> 100000/mm3, granulocytes \>1500/mm3) 3. No extramedullary disease. Relapse Criteria: 1. After CR: \>5% blasts in the bone marrow and/or peripheral blood 2. After partial remission (PR): increase of blasts cells in the marrow to \>50% of those during PR 3. Extramedullary disease confirmed cytologically or histologically.
measure
Duration of Remission
time Frame
1 year
description
The amount of energy absorbed per unit weight of the organ or tissue is called absorbed dose and is expressed in units of gray (Gy). One gray dose is equivalent to one joule radiation energy absorbed per kilogram of organ or tissue weight.
measure
Estimation of Absorbed Radiation Doses to Normal Organs, Marrow and Tumor
time Frame
Approximately day -20 to day -12 prior to transplant
description
Number of participants who are still alive after transplant with or without disease.
measure
Overall Survival
time Frame
Up to 5 years
description
Number of participants who developed acute GVHD post-transplant, aGVHD stages: Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
measure
Rates of Acute GvHD
time Frame
Up to 84 days post-transplant
description
Number of participants who has 100% donor chimerism within 100 days after transplant
measure
Rates of Donor Chimerism
time Frame
Up to 100 days post-transplant
description
Average number of days to ANC \>= 500 after transplant
measure
Rates of Engraftment
time Frame
Up to 84 days post-transplant
description
Transplant-related deaths within 100 days after transplant
measure
Rates of Non-relapse Mortality
time Frame
Within the first 100 days following transplant

Full study description

brief Summary: This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90 anti-cluster of differentiation 45 (CD45) monoclonal antibody BC8 (90Y-BC8) followed by donor stem cell transplant in treating patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) that is likely to come back or spread. Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body irradiation (TBI) before a donor peripheral blood stem cell (PBSC) or bone marrow transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies, such as 90Y-BC8, can find cancer cells and carry cancer-killing substances to them without harming normal 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 make an immune response against the body's normal cells. Giving FLU, 90Y-BC8, and TBI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
detailed Description: PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-DOTA-BC8 (90Y-BC8) when combined with FLU and 2 Gy TBI as a preparative regimen for patients aged \>= 18 with advanced AML, ALL, and high-risk MDS. SECONDARY OBJECTIVES: I. To determine disease response and duration of remission. II. To determine the rates of engraftment and donor chimerism resulting from this combined preparative regimen, and to correlate level of donor chimerism with estimated radiation doses delivered to hematopoietic tissues via antibody. OUTLINE: PREPARATIVE REGIMEN: Patients receive 90Y-BC8 via central line on approximately day -12 and FLU intravenously (IV) over 30 minutes on days -4 to -2. TRANSPLANTATION: Patients undergo TBI followed by allogeneic PBSC or bone marrow transplant on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive mycophenolate mofetil orally (PO) or IV every 12 hours on days 0-27 (for patients with related donors) or every 8 hours on days 0-40 with taper to day 96 (for patients with unrelated donors). Patients also receive cyclosporine PO or IV every 12 hours on days -3 to 56 (for patients with related donors) or 100 (for patients with unrelated donors) with taper to day 180. After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24 months, and then annually thereafter.

Source references

references

citation
Vo P, Gooley TA, Rajendran JG, Fisher DR, Orozco JJ, Green DJ, Gopal AK, Haaf R, Nartea M, Storb R, Appelbaum FR, Press OW, Pagel JM, Sandmaier BM. Yttrium-90-labeled anti-CD45 antibody followed by a reduced-intensity hematopoietic cell transplantation for patients with relapsed/refractory leukemia or myelodysplasia. Haematologica. 2020 Jun;105(6):1731-1737. doi: 10.3324/haematol.2019.229492. Epub 2019 Oct 3.
pmid
31582553
type
DERIVED

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice