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

3 december 2017 bijgewerkt door: Masonic Cancer Center, University of Minnesota

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

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.

Studie Overzicht

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

24

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

Niet ouder dan 60 jaar (Kind, Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Natural Killer Cell Kir Epitope
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.
Andere namen:
  • ATG
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).
Andere namen:
  • Fludara
Thiotepa 5 mg/kg/day intravenously (IV) over 4 hours on days -8, -7 (total dose 10 mg/kg).
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.
Andere namen:
  • PBSC
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.
Andere namen:
  • TBI

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of Disease-free Survival
Tijdsspanne: 1 Year
Number of patients alive and without disease at 1 year after transplant.
1 Year

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of Disease Relapse
Tijdsspanne: 1 Year
Number of patients with disease at 1 year.
1 Year
Incidence of Grade II-IV Acute Graft-vs-host Disease (GVHD)
Tijdsspanne: Day 100
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.
Day 100
Incidence of Chronic Graft-versus-host Disease (GVHD)
Tijdsspanne: 1 Year
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.
1 Year
Incidence of Graft Failure
Tijdsspanne: Day 100
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.
Day 100
Transplant-related Mortality
Tijdsspanne: 1 Year
Number of patients with treatment related death at 1 year post transplant.
1 Year
Overall Survival
Tijdsspanne: 1 Year
Number of patients who were deceased at 1 year post transplant.
1 Year

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juli 2005

Primaire voltooiing (Werkelijk)

1 mei 2011

Studie voltooiing (Werkelijk)

1 mei 2011

Studieregistratiedata

Eerst ingediend

25 oktober 2006

Eerst ingediend dat voldeed aan de QC-criteria

25 oktober 2006

Eerst geplaatst (Schatting)

26 oktober 2006

Updates van studierecords

Laatste update geplaatst (Werkelijk)

28 december 2017

Laatste update ingediend die voldeed aan QC-criteria

3 december 2017

Laatst geverifieerd

1 december 2017

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • 2004UC035
  • UMN-MT2004-04 (Andere identificatie: Blood and Marrow Transplantation Program)
  • UMN-0405M59662 (Andere identificatie: IRB, University of Minnesota)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op Myelodysplastische syndromen

  • The Champ Foundation
    Children's Hospital of Philadelphia; The Cleveland Clinic
    Werving
    Pearson-syndroom | Single Large Scale Mitochondrial DNA Deletion Syndromes (SLSMDS)
    Verenigde Staten

Klinische onderzoeken op anti-thymocyte globulin

3
Abonneren