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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).


Phase 1
50 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

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).


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.


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 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 >= 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) 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients who develop grades III/IV Bearman toxicity

Outcome Description:

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.

Outcome Time Frame:

Within the first 100 days following transplant

Safety Issue:

Yes

Principal Investigator

John Pagel

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2468.00

NCT ID:

NCT01300572

Start Date:

January 2012

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Neoplasms
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109