Donor Stem Cell Transplant in Treating Patients With Myeloid Cancer or Other Disease

This study has been completed.
Sponsor:
Collaborator:
Center for International Blood and Marrow Transplant Research
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00392782
First received: October 25, 2006
Last updated: November 6, 2012
Last verified: November 2012
  Purpose

RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When 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 antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with myeloid cancer or other disease.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Drug: thiotepa
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Incidence of Disease-free Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Number of patients alive and without disease at 1 year after transplant.


Secondary Outcome Measures:
  • Incidence of Disease Relapse [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Number of patients with disease at 1 year.

  • Incidence of Grade II-IV Acute Graft-vs-host Disease (GVHD) [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Number of patients with grade II-IV acute graft-versus-host disease at Day 100 post transplant. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. Grade I=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening.

  • Incidence of Chronic Graft-versus-host Disease (GVHD) [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Number of patients with chronic graft-versus-host disease at 1 year post transplant. Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack. Grade I=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening. Chronic GVHD is an extension of acute GVHD.

  • Incidence of Graft Failure [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
    Number of patients with graft failure is defined by lack of neutrophil engraftment by 100 days after transplant in patients surviving a minimum of 14 days.

  • Transplant-related Mortality [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Number of patients with treatment related death at 1 year post transplant.

  • Overall Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Number of patients who were deceased at 1 year post transplant.


Enrollment: 24
Study Start Date: July 2005
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Natural Killer Cell Kir Epitope Biological: anti-thymocyte globulin
Rabbit thymoglobulin will be given intravenously at a dose of 2.5 mg/kg on days -5,-4, -3, and -2. The first dose of thymoglobulin will be given over six (6) hours and subsequent doses over four (4) or more hours as tolerated or, per institutional anti-thymocyte globulin (ATG) administration guidelines.
Other Name: ATG
Drug: fludarabine phosphate
Fludarabine 40 mg/m^2/day intravenously (IV) over 30-60 minutes on days -7,-6,-5,-4,-3 (total dose 200 mg/m^2).
Other Name: Fludara
Drug: thiotepa
Thiotepa 5 mg/kg/day intravenously (IV) over 4 hours on days -8, -7 (total dose 10 mg/kg).
Procedure: peripheral blood stem cell transplantation
Peripheral Blood Stem Cell (PBSC) Infusion. All patients will receive granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC on day 0 (or day+1 when available) following CD34 cell selection for ex vivo T cell removal. PBSC is infused via a central venous catheter using blood infusion tubing.
Other Name: PBSC
Radiation: total-body irradiation
The total-body irradiation (TBI) will be given in 2 fractions of 400 cGy each administered on day -10 and -9 via anterior and posterior fields for a total dose of 800 cGy.
Other Name: TBI

Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • Determine the incidence of disease relapse at 1 year in patients treated with this regimen.
  • 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 [control]).

  • 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.

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392782

Locations
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Midwest Children's Cancer Center at Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Center for International Blood and Marrow Transplant Research
Investigators
Principal Investigator: Daniel J. Weisdorf, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00392782     History of Changes
Other Study ID Numbers: 2004UC035, UMN-MT2004-04, UMN-0405M59662
Study First Received: October 25, 2006
Results First Received: June 15, 2011
Last Updated: November 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Thiotepa
Fludarabine phosphate
Fludarabine
Vidarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 28, 2014