Know Cancer

forgot password

Hematopoietic Cell Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Radiolabeled DOTA-Biotin Pretargeted by BC8 Antibody-Streptavidin Conjugate

Phase 1
18 Years
Open (Enrolling)
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), Chronic Myelomonocytic Leukemia, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Ringed Sideroblasts, Refractory Cytopenia With Multilineage Dysplasia, Secondary Acute Myeloid Leukemia

Thank you

Trial Information

Hematopoietic Cell Transplantation for Patients With High-Risk Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), or Myelodysplastic Syndrome (MDS) Using Radiolabeled DOTA-Biotin Pretargeted by BC8 Antibody-Streptavidin Conjugate


I. To estimate the maximum tolerated dose (MTD) of radiation delivered via PRIT using BC8-SA
(BC8 antibody-streptavidin conjugate) when combined with fludarabine (FLU), 2 Gy total body
irradiation (TBI), cyclosporine (CSP), mycophenolate mofetil (MMF), and allogeneic
hematopoietic cell transplant (HCT) in patients who have advanced acute myeloid leukemia
(AML), acute lymphoblastic leukemia (ALL), or high risk myelodysplastic syndromes (MDS).


I. To estimate rates of immune reconstitution, engraftment, and donor chimerism resulting
from this combined preparative regimen.

II. To estimate rates of disease relapse, acute graft-versus-host disease (GvHD), and
day-100 disease-free survival in patients receiving PRIT using BC8-SA combined with FLU, 2
Gy TBI, CSP, MMF, and allogeneic HCT.

III. To assess biodistribution, serum half-life, urinary excretion, tissue localization, and
clearance of BC8-SA conjugate and DOTA-biotin.

IV. To assess the feasibility of yttrium y 90 (90Y)-DOTA-biotin to bind to BC8-SA conjugate
localized to hematolymphoid tissues.


Patients undergo pretargeted radioimmunotherapy comprising a test dose of BC8-SA conjugate
intravenously (IV) on day -22 and indium In 111(111In)-DOTA-biotin IV on day -20, followed
by a therapy dose of BC8-SA conjugate IV on day -14 and 90Y-DOTA-biotin IV on day -12.
Patients receive fludarabine phosphate IV on days -4 to -2. Patients undergo TBI and then
peripheral blood stem cell transplantation on day 0. Patients with matched related donors
receive cyclosporine IV on days -3 to 56 and taper to day 180 and mycophenolate mofetil
orally (PO) twice daily (BID) on days 0-27. Patients with matched unrelated donors receive
cyclosporine IV on days -3 to 100 and taper to day 180 and mycophenolate mofetil PO thrice
daily (TID) on days 0- 40 and taper to day 96.

After completion of study treatment, patients are followed up at 6, 9, 12, 18, and 24
months, and then periodically thereafter.

Inclusion Criteria:

- Patients with advanced AML or ALL defined as beyond first remission, primary
refractory disease, or evolved from myelodysplastic or myeloproliferative syndromes;
or patients with MDS expressed as refractory anemia with excess blasts (RAEB),
refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed
sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML)

- 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
nonmalignant 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
(test must be performed within 28 days prior to registration)

- Bilirubin < 2 times the upper limit of normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the
upper limit of normal

- Karnofsky score >= 70 or Eastern Cooperative Oncology Group (ECOG) =< 2

- Patients must have an expected survival of > 60 days and must be free of active

- 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) criteria for peripheral blood stem cell
(PBSC) donation; related donors should be matched by molecular methods at the
intermediate resolution level at HLA-A, B, C, and DRB1 according to Fred Hutchinson
Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level
at DQB1; unrelated donors should be identified using matching criteria that follows
the FHCRC standard practice guidelines limiting the study to eligible donors that are
allele matched for HLA-A, B, C, DRB1, and DQB1 (Grade 1), and accepting up to one
allele mismatch as per standard practice grade 2.1 for HLA-A, B, or C; PBSC is the
only permitted stem cell source

Exclusion Criteria:

- Circulating human anti-mouse antibody (HAMA) or human anti-streptavidin antibody

- Prior radiation to maximally tolerated levels to any critical normal organ

- Patients may not have symptomatic coronary artery disease and may not be on cardiac
medications for anti-arrhythmic or inotropic effects

- Patients with the following organ dysfunction:

- Left ventricular ejection fraction < 35%

- Corrected diffusion capacity of carbon monoxide (DLCO) < 35% and/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 seropositive for human immunodeficiency virus (HIV)

- Perceived inability to tolerate diagnostic or therapeutic procedures, particularly
treatment in radiation isolation

- Active central nervous system (CNS) leukemia

- Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin
[b-HCG] +)or breast feeding

- Fertile men and women unwilling to use contraceptives during and for 12 months post

- Patients may not use vitamin supplements containing biotin from the time of 1 week
prior to treatment until 1 week after completion of treatment with all PRIT

- Inability to understand or give an informed consent

Type of Study:


Study Design:

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

Outcome Measure:

Incidence of dose-limiting toxicities (DLT) (Grade III/IV Bearman) to determine MTD of radiation delivered to normal organ by pretargeted 90Y-DOTA-biotin

Outcome Description:

Conducted by the "two-stage" approach introduced by Storer. The MTD will be defined as the dose of 90Y-DOTA-biotin used in combination with the non-myeloablative HCT conditioning regimen that is associated with a Grade III/IV regimen related toxicity (RRT) or true DLT rate of 25%.

Outcome Time Frame:

Within 100 days post-transplant

Safety Issue:


Principal Investigator

John Pagel

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Food and Drug Administration

Study ID:




Start Date:

April 2010

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)
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Ringed Sideroblasts
  • Refractory Cytopenia With Multilineage Dysplasia
  • Secondary Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109