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Stem Cell Transplant for Immunologic or Histiocytic Disorders

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ClinicalTrials.gov Identifier: NCT00176865
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : April 14, 2017
Last Update Posted : December 28, 2017
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE September 12, 2005
First Posted Date  ICMJE September 15, 2005
Results First Submitted Date  ICMJE May 6, 2015
Results First Posted Date  ICMJE April 14, 2017
Last Update Posted Date December 28, 2017
Study Start Date  ICMJE August 2002
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2017)
Number of Subjects With Mixed Chimerism [ Time Frame: Day 100 ]
>10% Donor Cells at Day 100
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2005)
To demonstrate the safety and the ability to establish stable mixed chimerism (>10% donor cells at day 100) using a nonmyeloablative preparative regimen in a phase 2 pilot trial
Change History Complete list of historical versions of study NCT00176865 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2017)
  • Percentage of Donor Chimerism at 100 Days [ Time Frame: Day 100 ]
    The percent of recipient bone marrow and blood cells that are of donor origin.
  • Percentage of Donor Chimerism at 180 Days [ Time Frame: Day 180 ]
    The percent of recipient bone marrow and blood cells that are of donor origin.
  • Percentage of Donor Chimerism at 365 Days [ Time Frame: Day 365 ]
    The percent of recipient bone marrow and blood cells that are of donor origin.
  • Incidence of Grade 2-4 Acute Graft Versus Host Disease (aGVHD) [ Time Frame: Day 100 ]
    Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease.
  • Incidence of Grade 3-4 Acute Graft Versus Host Disease (aGVHD) [ Time Frame: Day 100 ]
    Acute graft versus host disease (aGVHD) is a reaction occurring within the first 100 days after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs. The severity of aGVHD is graded on a scale of 1 - 4 with the highest number representing the most severe disease.
  • Incidence of Chronic Graft Versus Host Disease (cGVHD) [ Time Frame: 6 months and 1 year ]
    Chronic graft versus host disease (cGVHD) is a reaction which typically develops 3 to 6 months after transplant where the T- cells of the donor graft attacks the recipient's (host's) skin, GI tract, liver and other organs.
  • Number of Subjects Alive at 100 Days [ Time Frame: Day 100 ]
  • Number of Subjects Alive at One Year [ Time Frame: Day 365 ]
  • Compare Quality of Life (QOL) [ Time Frame: Pretransplant, 1 year, 2 years and 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2005)
  • Determine the incidence of chimerism at 100 days, 6 months and 1 year.
  • Determine the incidence of grade 2-4 and 3-4 acute GVHD at 100 days.
  • Determine the incidence of chronic GVHD at 6 months and 1 year.
  • Compare the quality of life (QOL) at 1, 2 and 5 years with the pre-transplant assessment.
  • Determine overall survival at 100 days and 1 year.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stem Cell Transplant for Immunologic or Histiocytic Disorders
Official Title  ICMJE Allogeneic Hematopoietic Stem Cell Transplant for Patients With Immunologic or Histiocytic Disorders Using a Non-Myeloablative Preparative Regimen to Achieve Stable Mixed Chimerism
Brief Summary

This study tests the clinical outcomes of a preparative regimen of fludarabine (FLU), anti-thymocyte globulin (ATG)/or Campath, and melphalan; followed by hematopoietic stem cell transplant, and a post transplant regimen of Cyclosporin A (CsA) in patients with immunologic or histiocytic disorders. The researchers hypothesize that this regimen will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease (GVHD).

Patients will be randomized biologically into one of 3 arms based upon donor availability: (a) human leukocyte antigen (HLA) genotypic matched sibling donor, (b) HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor, (c) two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord).

Detailed Description

Prior to transplantation, subjects will receive Melphalan, Fludarabine and Anti-Thymocyte Globulin (ATG) or Campath. These three drugs are being given to subjects to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.

After stem cell transplantation, subjects will be given Cyclosporin A (CsA) and mycophenolate mofetil (MMF) to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hemophagocytic Lymphohistiocytosis
  • X-Linked Lymphoproliferative Disorders
  • Chediak-Higashi Syndrome
  • Griscelli Syndrome
  • Immunologic Deficiency Syndromes
  • Langerhans-Cell Histiocytosis
Intervention  ICMJE
  • Procedure: Stem Cell Transplant
    IV on Day 0
    Other Name: hematopoietic stem cell transplant
  • Drug: Fludarabine
    30mg/m^2 IV Day -7 through Day -3
    Other Name: Fludara
  • Drug: Melphalan
    140 mg/m^2 IV Day -1
    Other Name: Alkeran
  • Drug: Anti-thymocyte globulin (ATG)
    30 mg/kg IV Day -5 through Day -1
    Other Name: ATGAM
  • Drug: Campath 1H
    0.2 mg/kg IV X 5 days (used as an alternative to Anti-thymocyte globulin (ATG) if unable to tolerate ATG) Day -10 through Day -6
    Other Name: Alemtuzumab
  • Drug: Cyclosporin A
    2.5 mg/kg IV every 12 hours (adults) or every 8 hours (children <40 kg) maintaining a level of >200mg/L Day -3 until Day +180 when, if no GVHD, the dose will be tapered 10% per week beginning on day 181
  • Drug: Mycophenolate mofetil
    15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present
    Other Name: CellCept
  • Drug: Intravenous immunoglobulin (IVIG)
    500 mg/kg IV weekly beginning on Day +7 until Day +100
Study Arms  ICMJE
  • Active Comparator: Arm 1 - Matched sibling donor
    Stem Cell Transplant: human leukocyte antigen (HLA) genotypic matched sibling donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
    Interventions:
    • Procedure: Stem Cell Transplant
    • Drug: Fludarabine
    • Drug: Melphalan
    • Drug: Anti-thymocyte globulin (ATG)
    • Drug: Campath 1H
    • Drug: Cyclosporin A
    • Drug: Mycophenolate mofetil
    • Drug: Intravenous immunoglobulin (IVIG)
  • Active Comparator: Arm 2 - Matched unrelated donor
    Stem Cell Transplant: HLA phenotypic matched unrelated peripheral blood stem cell (PBSC) donor and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
    Interventions:
    • Procedure: Stem Cell Transplant
    • Drug: Fludarabine
    • Drug: Melphalan
    • Drug: Anti-thymocyte globulin (ATG)
    • Drug: Campath 1H
    • Drug: Cyclosporin A
    • Drug: Mycophenolate mofetil
    • Drug: Intravenous immunoglobulin (IVIG)
  • Active Comparator: Arm 3 - Mismatched double cord donors
    Stem Cell Transplant: two HLA 0-2 antigen mismatched unrelated cord blood donors (double cord) and pre-treatment with fludarabine, melphalan, anti-thymocyte globulin or Campath 1H and post-treatment with Cyclosporin A, mycophenolate mofetil and Intravenous immunoglobulin (IVIG)
    Interventions:
    • Procedure: Stem Cell Transplant
    • Drug: Fludarabine
    • Drug: Melphalan
    • Drug: Anti-thymocyte globulin (ATG)
    • Drug: Campath 1H
    • Drug: Cyclosporin A
    • Drug: Mycophenolate mofetil
    • Drug: Intravenous immunoglobulin (IVIG)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 3, 2017)
19
Original Enrollment  ICMJE
 (submitted: September 12, 2005)
30
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patients with immunodeficiencies or histiocytic disorders 0-35 years of age with an acceptable stem cell donor and disease characteristic defined by the following:

  • Patients with histocytic disorders (hemophagocytic lymphohistiocytosis of any etiology and refractory Langerhans cell histiocytosis) who do not meet eligibility criteria for a myeloablative transplant procedure
  • Patients with immunodeficiency disorders in whom residual immune function may not require a fully myeloablative preparative regimen or patient is ineligible for standard myeloablative preparative regimen (any form of severe combined immunodeficiency [SCID], or other immunodeficiency with T cell defect)
  • Patients with immunodeficiency disorders that have had poor outcome with myeloablative stem cell transplants (including, but not limited to, common variable immunodeficiency [CVID], Wiskott Aldrich Syndrome [WAS] if > 5 years of age, ataxia telangiectasia)
  • Patients with immunodeficiencies or histocytic disorders that require a second stem cell transplant (SCT) for any reason

Exclusion Criteria:

  • Karnofsky or Lansky performance score <70
  • Glomerular filtration rate (GFR)<30% predicted
  • Cardiac function <50% normal by echocardiogram
  • Serum creatinine > 2x normal for age/weight
  • Pregnant or lactating females
  • Active serious infection that has not had an adequate course of therapy pre-SCT. Any patient with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) or human immunodeficiency virus (HIV) seropositivity
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 35 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00176865
Other Study ID Numbers  ICMJE MT2002-12
0207M29448 ( Other Identifier: IRB, University of Minnesota )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Angela Smith, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP