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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2019-11-22

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Myelomonocytic Leukemia Previously Treated Myelodysplastic Syndrome Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Refractory Anemia With Excess Blasts Secondary Acute Myeloid Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Y-90-BC8 & Allogeneic Transplant

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.

Group Type EXPERIMENTAL

Allogeneic Bone Marrow Transplantation

Intervention Type PROCEDURE

Undergo allogeneic bone marrow transplant

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo allogeneic PBSC or bone marrow transplant

Cyclosporine

Intervention Type DRUG

Given PO or IV

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Indium In 111 Anti-CD45 Monoclonal Antibody BC8

Intervention Type BIOLOGICAL

Given IV (dosimetric dose)

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Mycophenolate Mofetil

Intervention Type DRUG

Given PO or IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo allogeneic PBSC transplant

Pharmacological Study

Intervention Type OTHER

Correlative studies

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8

Intervention Type RADIATION

Given via central line (therapeutic dose)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Allogeneic Bone Marrow Transplantation

Undergo allogeneic bone marrow transplant

Intervention Type PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic PBSC or bone marrow transplant

Intervention Type PROCEDURE

Cyclosporine

Given PO or IV

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Indium In 111 Anti-CD45 Monoclonal Antibody BC8

Given IV (dosimetric dose)

Intervention Type BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Mycophenolate Mofetil

Given PO or IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo allogeneic PBSC transplant

Intervention Type PROCEDURE

Pharmacological Study

Correlative studies

Intervention Type OTHER

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8

Given via central line (therapeutic dose)

Intervention Type RADIATION

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Allo BMT Allogeneic BMT allogeneic stem cell transplantation HSC HSCT 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Gengraf Neoral OL 27-400 Sandimmun Sandimmune SangCya 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 In 111 MOAB BC8 In 111 Monoclonal Antibody BC8 Indium In 111 Monoclonal Antibody BC8 monoclonal antibody BC8, indium In 111 Cellcept MMF PBPC transplantation Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplantation TOTAL BODY IRRADIATION Whole-Body Irradiation 90Y Anti-CD45 MoAb BC8

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Brenda Sandmaier

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Brenda Sandmaier

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED

PMID: 31582553 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document