Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome

This study is currently recruiting participants.
Verified March 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01300572
First received: February 15, 2011
Last updated: March 10, 2014
Last verified: March 2014

February 15, 2011
March 10, 2014
January 2012
December 2016   (final data collection date for primary outcome measure)
Proportion of patients who develop grades III/IV Bearman toxicity [ Time Frame: Within the first 100 days following transplant ] [ Designated as safety issue: Yes ]
Assessed according to Bearman scale for Regimen-Related Toxicities. Two-parameter logistic model will be fit to the data, thereby generating a dose-response curve based on the observed toxicity rate at the various dose levels visited.
  • Proportion of patients who develop grades III/IV Bearman toxicity [ Time Frame: Within the first 100 days following transplant ] [ Designated as safety issue: Yes ]
    Assessed according to Bearman scale for Regimen-Related Toxicities
  • Rates of non-relapse mortality [ Time Frame: Within the first 100 days following transplant ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01300572 on ClinicalTrials.gov Archive Site
  • Rates of engraftment [ Time Frame: Up to 84 days post-transplant ] [ Designated as safety issue: No ]
  • Rates of donor chimerism [ Time Frame: Up to 84 days post-transplant ] [ Designated as safety issue: No ]
  • Rates of non-relapse mortality [ Time Frame: Within the first 100 days following transplant ] [ Designated as safety issue: No ]
  • Rates of acute GvHD [ Time Frame: Up to 84 days post-transplant ] [ Designated as safety issue: No ]
  • Achievement of remission [ Time Frame: Prior to day 100 post-transplant ] [ Designated as safety issue: No ]
  • Duration of remission [ Time Frame: Prior to day 100 post-transplant ] [ Designated as safety issue: No ]
  • Duration of remission [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Estimation of absorbed radiation doses to normal organs, marrow and tumor [ Time Frame: Approximately day -20 to day -12 prior to transplant ] [ Designated as safety issue: No ]
  • Rates of engraftment [ Time Frame: At days +28, +56, and +84 ] [ Designated as safety issue: No ]
  • Achievement of remission [ Time Frame: Response assessed prior to day 100 post transplant; duration of remission assessed at 6, 9, 12, 18, 24 months, then annually throughout survival ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Assessed at 6, 9, 12, 18, 24 months, then annually throughout survival ] [ Designated as safety issue: No ]
  • Estimation of absorbed radiation doses to normal organs, marrow and tumor [ Time Frame: Prior to transplant ] [ Designated as safety issue: No ]
  • Rates of donor chimerism [ Time Frame: At baseline and days +28, +56, and +84 ] [ Designated as safety issue: No ]
  • Duration of remission [ Time Frame: Response assessed prior to day 100 post transplant; duration of remission assessed at 6, 9, 12, 18, 24 months, then annually throughout survival ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: Assessed at 6, 9, 12, 18, 24 months, then annually throughout survival ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome
A Study Evaluating Escalating Doses of 90Y-DOTA-BC8 (Anti-CD45) Antibody Followed by Allogeneic Stem Cell Transplantation for High-Risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS).

This phase I trial studies the side effects and maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody BC8 (90Y-BC8) followed by donor peripheral blood stem cell transplant (PBSC) in treating patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body irradiation (TBI) before a donor PBSC 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.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of radiation delivered via 90Y-DOTA-BC8 (90Y-BC8) antibody (Ab) when combined with FLU and 2 Gy TBI as a preparative regimen for patients aged >= 50 with advanced AML 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 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 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 orally (PO) 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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Refractory Anemia With Excess Blasts
  • Secondary Acute Myeloid Leukemia
  • Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
    Given via central line (therapeutic dose)
    Other Names:
    • 90Y anti-CD45 MAb BC8
    • 90Y anti-CD45 MoAb BC8
  • Biological: indium In 111 anti-CD45 monoclonal antibody BC8
    Given IV (dosimetric dose)
    Other Names:
    • In 111 MOAB BC8
    • In 111 monoclonal antibody BC8
    • In111 MOAB BC8
    • indium In 111 MOAB BC8
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • Fludara
  • Drug: cyclosporine
    Given PO or IV
    Other Names:
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Drug: mycophenolate mofetil
    Given PO or IV
    Other Names:
    • Cellcept
    • MMF
  • Radiation: total-body irradiation
    Undergo TBI
    Other Name: TBI
  • Procedure: peripheral blood stem cell transplantation
    Undergo allogeneic PBSC transplant and allogeneic hematopoietic stem cell transplant
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
  • Procedure: bone marrow transplantation
    Undergo BMT
    Other Names:
    • BMT
    • transplantation, bone marrow
Experimental: Treatment (radiolabeled monoclonal antibody, allogeneic HSCT)

PREPARATIVE REGIMEN: Patients receive 90Y-BC8 via central line on 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 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 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.

Interventions:
  • Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
  • Biological: indium In 111 anti-CD45 monoclonal antibody BC8
  • Drug: fludarabine phosphate
  • Drug: cyclosporine
  • Drug: mycophenolate mofetil
  • Radiation: total-body irradiation
  • Procedure: peripheral blood stem cell transplantation
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
  • Procedure: bone marrow transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
Not Provided
December 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have advanced AML or high-risk MDS meeting one of the following descriptions:

    • AML beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen)
    • AML representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens)
    • AML evolved from MDS or myeloproliferative syndromes; or
    • MDS expressed as refractory anemia with excess blasts (RAEB)
  • Patients not in remission must have cluster of differentiation (CD)45-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 >= 50 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
  • Bilirubin < 2 times the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine transaminase (ALT) < 2 times the upper limit of normal
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • 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:

    • Sibling donor; a patient and sibling donor should be matched for HLA-A, B, C, DRB1 and DQB1 by an intermediate resolution deoxyribonucleic acid (DNA)-based method
    • Unrelated donor; an unrelated donor and recipient should be typed by a high resolution DNA-based method, and ideally matched for HLA-A, B, C, DRB1 and DQB1 alleles, or if there is only a single locus disparity mismatched for an HLA-DQB1 antigen or allele; an unrelated donor may also be mismatched for any single 1) one HLA-A, B or C antigen or allele, or 2) a single DR antigen or 3) a single DQ antigen or allele or 4) HLA-DRB1 allele (with or without matching for HLA-DQB1)
  • 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 gonadotrophin [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
Both
50 Years and older
No
Not Provided
United States
 
NCT01300572
2468.00, NCI-2011-00150, P30CA015704, P01CA044991, 2468.00, P01CA044991, P30CA015704
No
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: John Pagel Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP