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NCT Number: NCT00176865

Stem Cell Transplant for Immunologic or Histiocytic Disorders

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).

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Key information

Conditions

Hemophagocytic Lymphohistiocytosis Albinism Chediak-Higashi Syndrome Congenital, Hereditary, and Neonatal Diseases and Abnormalities Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Griscelli Syndrome Hematologic Diseases Hemic and Lymphatic Diseases Histiocytosis Histiocytosis, Langerhans-Cell Histiocytosis, Non-Langerhans-Cell Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Langerhans-Cell Histiocytosis Leukocyte Disorders Lung Diseases Lung Diseases, Interstitial Lymphatic Diseases Lymphohistiocytosis, Hemophagocytic Lymphoproliferative Disorders Phagocyte Bactericidal Dysfunction Primary Immunodeficiency Diseases Respiratory Tract Diseases X-Linked Lymphoproliferative Disorders

Age range

Up to 35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Masonic Cancer Center University of Minnesota

Minneapolis, Minnesota, 55455, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Stem Cell Transplant

Procedure

IV on Day 0

Other names: hematopoietic stem cell transplant

Fludarabine

Drug

30mg/m^2 IV Day -7 through Day -3

Other names: Fludara

melphalan

Drug

140 mg/m^2 IV Day -1

Other names: Alkeran

Anti-thymocyte globulin (ATG)

Drug

30 mg/kg IV Day -5 through Day -1

Other names: ATGAM

Campath 1H

Drug

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 names: Alemtuzumab

cyclosporin A

Drug

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

Mycophenolate mofetil

Drug

15 mg/kg IV or orally bid and discontinued on Day +45 unless GVHD is present

Other names: CellCept

Intravenous immunoglobulin (IVIG)

Drug

500 mg/kg IV weekly beginning on Day +7 until Day +100

Primary outcomes

  1. Number of Subjects With Mixed Chimerism

    Time frame: Day 100

    >10% Donor Cells at Day 100

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Number of Subjects Alive at 100 Days

    Time frame: Day 100

  8. Number of Subjects Alive at One Year

    Time frame: Day 365

  9. Compare Quality of Life (QOL)

    Time frame: Pretransplant, 1 year, 2 years and 5 years

Sponsors and collaborators

Lead sponsor

Masonic Cancer Center, University of Minnesota

Other

Registry information

Official study title

Allogeneic Hematopoietic Stem Cell Transplant for Patients With Immunologic or Histiocytic Disorders Using a Non-Myeloablative Preparative Regimen to Achieve Stable Mixed Chimerism

Important dates

Study start
2002
Primary completion
2012
Study completion
2014
First posted
Sep 15, 2005
Registry last updated
Dec 28, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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