Stem Cell Transplant for Immunologic or Histiocytic Disorders

December 3, 2017 updated by: Masonic Cancer Center, University of Minnesota

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 35 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • hematopoietic stem cell transplant
Drug: Fludarabine
30mg/m^2 IV Day -7 through Day -3
Other Names:
  • Fludara
Drug: Melphalan
140 mg/m^2 IV Day -1
Other Names:
  • Alkeran
Drug: Anti-thymocyte globulin (ATG)
30 mg/kg IV Day -5 through Day -1
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • hematopoietic stem cell transplant
Drug: Fludarabine
30mg/m^2 IV Day -7 through Day -3
Other Names:
  • Fludara
Drug: Melphalan
140 mg/m^2 IV Day -1
Other Names:
  • Alkeran
Drug: Anti-thymocyte globulin (ATG)
30 mg/kg IV Day -5 through Day -1
Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • hematopoietic stem cell transplant
Drug: Fludarabine
30mg/m^2 IV Day -7 through Day -3
Other Names:
  • Fludara
Drug: Melphalan
140 mg/m^2 IV Day -1
Other Names:
  • Alkeran
Drug: Anti-thymocyte globulin (ATG)
30 mg/kg IV Day -5 through Day -1
Other Names:
  • 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 Names:
  • 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 Names:
  • CellCept
Drug: Intravenous immunoglobulin (IVIG)
500 mg/kg IV weekly beginning on Day +7 until Day +100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Mixed Chimerism
Time Frame: Day 100
>10% Donor Cells at Day 100
Day 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 100
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.
Day 180
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.
Day 365
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.
Day 100
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.
Day 100
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.
6 months and 1 year
Number of Subjects Alive at 100 Days
Time Frame: Day 100
Day 100
Number of Subjects Alive at One Year
Time Frame: Day 365
Day 365
Compare Quality of Life (QOL)
Time Frame: Pretransplant, 1 year, 2 years and 5 years
Pretransplant, 1 year, 2 years and 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2002

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

August 1, 2014

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Actual)

December 28, 2017

Last Update Submitted That Met QC Criteria

December 3, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MT2002-12
  • 0207M29448 (Other Identifier: IRB, University of Minnesota)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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