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Trial record 8 of 12 for:    "X-linked lymphoproliferative disease"

Stem Cell Transplant for Immunologic or Histiocytic Disorders

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00176865
First received: September 12, 2005
Last updated: March 3, 2017
Last verified: October 2014
  Purpose

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).


Condition Intervention Phase
Hemophagocytic Lymphohistiocytosis X-Linked Lymphoproliferative Disorders Chediak-Higashi Syndrome Griscelli Syndrome Immunologic Deficiency Syndromes Langerhans-Cell Histiocytosis 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) Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With Immunologic or Histiocytic Disorders Using a Non-Myeloablative Preparative Regimen to Achieve Stable Mixed Chimerism

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Subjects With Mixed Chimerism [ Time Frame: Day 100 ]
    >10% Donor Cells at Day 100


Secondary Outcome Measures:
  • 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 ]

Enrollment: 19
Study Start Date: August 2002
Study Completion Date: August 2014
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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
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)
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
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)
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

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.

  Eligibility

Ages Eligible for Study:   up to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00176865

Locations
United States, Minnesota
Masonic Cancer Center University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Angela Smith, MD Masonic Cancer Center, University of Minnesota
  More Information

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00176865     History of Changes
Other Study ID Numbers: MT2002-12
0207M29448 ( Other Identifier: IRB, University of Minnesota )
Study First Received: September 12, 2005
Results First Received: May 6, 2015
Last Updated: March 3, 2017

Keywords provided by Masonic Cancer Center, University of Minnesota:
Stem cell transplant
immunodeficiency
donor lymphocyte infusion

Additional relevant MeSH terms:
Disease
Syndrome
Lymphoproliferative Disorders
Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Langerhans-Cell
Histiocytosis
Chediak-Higashi Syndrome
Immunologic Deficiency Syndromes
Pathologic Processes
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Histiocytosis, Non-Langerhans-Cell
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Fludarabine
Fludarabine phosphate
Alemtuzumab
Mycophenolic Acid
Melphalan
Cyclosporine
Cyclosporins
Mycophenolate mofetil
Antilymphocyte Serum
Immunoglobulins
Antibodies

ClinicalTrials.gov processed this record on June 28, 2017