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A Multicenter, Prospective Trial to Evaluate the Role of NK Cell KIR Epitope Mismatch on Mortality and Disease Relapse in T-Cell Depleted Hematopoietic Stem Cell Transplantation From HLA-C Mismatched, Unrelated Donors for Myeloid Malignancies

Phase 2
60 Years
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information

A Multicenter, Prospective Trial to Evaluate the Role of NK Cell KIR Epitope Mismatch on Mortality and Disease Relapse in T-Cell Depleted Hematopoietic Stem Cell Transplantation From HLA-C Mismatched, Unrelated Donors for Myeloid Malignancies



- Determine the incidence of disease-free survival at 1 year in patients with acute or
chronic myeloid leukemias undergoing T-cell-depleted hematopoietic stem cell
transplantation from HLA-C mismatched, unrelated donors.


- Determine the incidence of disease relapse at 1 year in patients treated with this

- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days
and chronic GVHD at 1 year in these patients.

- Determine the incidence of graft failure at day 100.

- Determine the transplant-related mortality of these patients at 1 year.

- Determine the overall survival of these patients at 1 year.

OUTLINE: This is a prospective, multicenter study. Patients are stratified according to
killer-cell immunoglobulin-like receptors (KIR) epitope mismatch (yes [experimental] vs no

- Myeloablative preparative regimen: Patients undergo total body irradiation twice daily
on days -10 and -9 and receive thiotepa intravenously (IV) over 4 hours on days -8 and
-7, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and antithymocyte
globulin IV over 4-6 hours on days -5 to -2.

- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo
filgrastim (G-CSF)-mobilized, T-cell-depleted, CD34+-selected allogeneic PBSC
transplantation on day 0.

After completion of study treatment, patients are followed periodically for at least 1 year.

Inclusion Criteria:

- Primary acute myeloid leukemia (AML)

- First complete remission (CR) with high risk features as defined by: failure to
achieve remission by day 21 after induction chemotherapy, or the presence of
chromosomal abnormalities involving any of the following: -5/de (5q),
-7/del(7q), inversion 3q, abnormalities of 11q23, 20q, 21q, del(9q),
translocation 6;9, translocation 9;22, abnormalities of 17p, or complex
karyotype with > or = 3 abnormalities. Complete remission is defined as < 5%
blasts in the marrow.

- Second CR or subsequent in remission

- Refractory or relapsed disease with absolute peripheral blood blasts < 2000/mcL

- Secondary AML in remission or relapse

- Chronic myelogenous leukemia (CML) in accelerated or blast phase

- Accelerated phase is defined by any one of the following:

- Blasts 10% to 19% of peripheral blood white cells or bone marrow cells

- Peripheral blood basophils at least 20%

- Persistent thrombocytopenia (<100 x 10^9/L) unrelated to therapy, or
persistent thrombocytosis (>1000 x 10^9/L) unresponsive to therapy

- Increasing spleen size and increasing white blood cell (WBC) count
unresponsive to therapy

- Cytogenetic evidence of clonal evolution (i.e., the appearance of an
additional genetic abnormality that was not present in the initial specimen
at the time of diagnosis of chronic phase CML)

- Resistance to tyrosine kinase inhibitors (imatinib or other) defined as no
complete cytogenetic response even if the above criteria are not met.

- Blast phase is defined by either of the following:

- Blasts 20% or more of peripheral blood white cells or bone marrow cells

- Extramedullary blast proliferation

- Large foci or clusters of blasts in bone marrow biopsy

- Primary myelodysplastic syndrome (MDS) with an IPSS score >1

- Secondary MDS with any international prostate symptom score (IPSS)

- Age ≤60 years

- Co-Morbidity score 0-2

- At least 35 days following start of preceding leukemia induction therapy

Exclusion Criteria:

- Patients for whom a suitable HLA genotypically identical sibling or fully matched
HLA-A, -B, -C, and -DRB1 unrelated donor is available.

- Patients greater than 60 years of age.

- Hypersensitivity to thymoglobulin.

- Symptomatic uncontrolled coronary artery disease or congestive heart failure.

- Hepatic disease with transaminases or bilirubin > 2 times upper limit of normal (ULN)
except for isolated hyperbilirubinemia attributed to Gilbert's syndrome.

- Severe hypoxemia with room air - Partial Pressure of Oxygen in Arterial Blood -
(PAO2) < 70, supplemental oxygen-dependence, or carbon monoxide diffusing capacity
(DLCO) < 50% predicted.

- Impaired renal function with creatinine > 2 times upper limit of normal (ULN) or
creatinine clearance measured by 24-hour urine collection < 50% normal for age,
gender, and weight.

- Patients with central nervous system (CNS) involvement with disease refractory to
intrathecal chemotherapy.

- Patients who are human immunodeficiency virus (HIV) seropositive.

- Patients who are pregnant or breast-feeding.

- Patients with active infections that are untreated, or failing to respond to
appropriate therapy.

- Karnofsky performance status < 50%.

- Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical
cord blood transplant.

- Inability to provide informed consent.

- Co-morbidity score >2

- Less than 35 days from start of previous leukemia induction therapy

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 Disease-free Survival

Outcome Description:

Number of patients alive and without disease at 1 year after transplant.

Outcome Time Frame:

1 Year

Safety Issue:


Principal Investigator

Daniel J. Weisdorf, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Food and Drug Administration

Study ID:




Start Date:

July 2005

Completion Date:

May 2011

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia in remission
  • childhood acute myeloid leukemia in remission
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • 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)
  • recurrent adult acute myeloid leukemia
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • childhood chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • secondary myelodysplastic syndromes
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia



Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
Midwest Children's Cancer Center at Children's Hospital of Wisconsin Milwaukee, Wisconsin  53226
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana  46202-5289
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis St. Louis, Missouri  63110
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240
Moffitt Cancer Center Tampa, Florida  33612