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T-Cell Depletion and Stem Cell Transplant for Immune Deficiencies and Histiocytic Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00176826
Recruitment Status : Terminated (Replaced by another protocol)
First Posted : September 15, 2005
Results First Posted : April 28, 2014
Last Update Posted : January 23, 2018
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
The hypothesis is to determine if a preparative regimen of busulfan, cyclophosphamide, and antithymocyte globulin (ATG) plus allogeneic stem cell transplantation will be effective in the treatment of immune deficiencies and histiocytic disorders.

Condition or disease Intervention/treatment Phase
Hemophagocytic Lymphohistiocytosis X-Linked Lymphoproliferative Disorders Chediak-Higashi Syndrome Griscelli Syndrome Immunologic Diseases Langerhans-Cell Histiocytosis Hematologic Diseases Procedure: Stem Cell Transplant Drug: Myeloablative conditioning regimen Phase 2 Phase 3

Detailed Description:

Subjects will begin chemotherapy as a preparative regimen, which is intended to completely eliminate their defective immune system and bone marrow. The preparative regimen consists of the chemotherapy drugs (busulfan, cyclophosphamide, and antithymocyte globulin (ATG)).

Transplantation: subjects will then have a source of blood stem cells (bone marrow) from their donor administered into their catheter. Medication will be given to help prevent Graft-Versus Host Disease (GVHD). The ATG will help to deplete the donor stem cells of the type of cells that can cause GVHD and will also help to promote engraftment of the new stem cells.

Recovery Phase: The second phase of treatment consists of a period after transplantation during which we wait for the return of bone marrow function. This usually takes two to four weeks. Subjects will be given a blood cell growth factor, G-CSF, to help speed recovery of the white blood cells and potentially decrease the risk of infection and decrease the time until the bone marrow recovers.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: In-vivo T-cell Depletion and Hematopoietic Stem Cell Transplantation for Life-Threatening Immune Deficiencies and Histiocytic Disorders
Study Start Date : September 2000
Actual Primary Completion Date : August 2012
Actual Study Completion Date : August 2015

Arm Intervention/treatment
Experimental: Intent-To-Treat
Patients who were treated with chemotherapies (myeloablative conditioning regimen) and stem cell transplant. Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant.
Procedure: Stem Cell Transplant
Infusion of hematopoietic stem cells (bone marrow, cord blood, peripheral blood stem cells) following myeloablative conditioning regimen.
Other Name: HSCT

Drug: Myeloablative conditioning regimen
Busulfan intravenously for 4 days followed by cyclophosphamide intravenously for 4 days. Rabbit ATG is given intravenously for 4 doses pre-transplant.
Other Names:
  • Busulfex
  • Cytoxan
  • ATG

Primary Outcome Measures :
  1. Time to Transplant Engraftment [ Time Frame: Day 100 Post Transplant ]

Secondary Outcome Measures :
  1. Number of Patients With Treatment Related Mortality. [ Time Frame: Day 100 Post Transplant ]
  2. Number of Patients Surviving (Disease-free) [ Time Frame: 1 year ]
  3. Number of Patients With Grade II-IV Graft-Versus-Host Disease (GVHD) [ Time Frame: Day 100 Post Transplant ]
  4. Number of Patients With Graft Failure [ Time Frame: Day 100 Post transplant ]
  5. Number of Patients With III-IV Graft-Versus-Host Disease (GVHD) [ Time Frame: Day 100 Post Transplant ]
  6. Number of Patients Surviving (Disease-free) [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Any patient from birth to < 55 years of age fulfilling the following criteria will be eligible for this study.
  • Patients meeting clinical diagnostic criteria for Hemophagocytic Lymphohistiocytosis (HLH)
  • Patients meeting clinical diagnostic criteria or genetic diagnosis of X-linked lymphoproliferative disorder (XLP) and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT.
  • Patients with Chediak-Higashi Syndrome who meet the following diagnostic criteria and whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V of the study protocol.
  • Patients with Viral Associated Hemophagocytic Syndrome (VAHS) - if relapsed after other therapy or supportive care. Diagnostic criteria as above for HLH. Disease status must be ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V. It is cautioned that many patients with HLH or familial hemophagocytic lymphohistiocytosis (FHL) will have a viral infection at time of initial presentation and may therefore be misdiagnosed as having VAHS.
  • Griscelli Syndrome
  • Primary immune deficiencies with non-genotypic identical donors only.
  • Progressive Langerhans cell histiocytosis unresponsive to standard therapy.
  • Other non-malignant hematological disorders in which stem cell transplant with a myeloablative regimen is indicated.
  • Diamond Blackfan Anemia if transfusion dependent
  • Schwachman Diamond Syndrome: with cytopenias or transformation to myelodysplastic syndrome (MDS)
  • Kostman's Syndrome (if ANC <500 without GCSF support, or transformation to MDS)
  • Congenital dyserythropoietic anemia if transfusion dependent
  • Amegakaryocytic thrombocytopenia if baseline platelet counts <20,000 or requiring transfusions.
  • Cardiac, hepatic, renal and pulmonary function deemed adequate for high dose chemotherapy with stem cell rescue as per institutional standards. General guidelines are as follows:

    • Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be > 40% and must improve with exercise, or shortening fraction by echocardiogram must be within institutional normals
    • Hepatic: < 3 x normal SGOT and < 2.5 mg/dL serum bilirubin
    • Renal: Serum creatinine within normal range, or if serum creatinine outside normal range then creatinine clearance or glomerular filtration study should be > 50% of normal.
    • Pulmonary: Asymptomatic or, if symptomatic, diffusing capacity of the lung for carbon monoxide (DLCO) > 45% of predicted (corrected for hemoglobin). For children unable to perform pulmonary function testing, then oxygen saturation should be >95%.
  • Availability of a suitable allogeneic bone marrow donor as per current institutional guidelines for non-T cell depleted hematopoietic stem cell transplant (HSCT).
  • Patients who have undergone previous stem cell transplant (SCT) and failed engraftment or who had relapse of their disease are considered eligible if they meet other eligibility criteria and if the second SCT would occur 6 months or more after the first. If the first SCT preparative regimen was of a non-myeloablative intensity then the second SCT could be performed earlier when the acute toxicity from that procedure was resolved.

Exclusion Criteria:

  • Patients who are moribund or whose life expectancy is severely limited by disease other than their underlying disorder. Karnofsky performance status < 70% or Lansky < 50% for patients < 16 years.
  • Patients with hemophagocytic disorders secondary to underlying malignancy.
  • Patients who have ACTIVE/UNSTABLE disease as defined in Appendix V.
  • Significant active infections, including Human Immunodeficiency Virus (HIV).
  • Age > 55 years.
  • Not providing informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00176826

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United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
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Principal Investigator: Angela Smith, MD University of Minnesota Medical Center
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Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT00176826    
Obsolete Identifiers: NCT00973843
Other Study ID Numbers: UMN-MT2000-21
0010M66781 ( Other Identifier: Institutional Review Board, University of Minnesota )
First Posted: September 15, 2005    Key Record Dates
Results First Posted: April 28, 2014
Last Update Posted: January 23, 2018
Last Verified: May 2015
Keywords provided by Masonic Cancer Center, University of Minnesota:
Stem Cell Transplant
T-cell depletion
immune deficiencies
Busulfan pharmacokinetics
Non-Malignant Hematological Disorders
Additional relevant MeSH terms:
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Histiocytosis, Langerhans-Cell
Chediak-Higashi Syndrome
Lymphoproliferative Disorders
Hematologic Diseases
Lymphohistiocytosis, Hemophagocytic
Immunologic Deficiency Syndromes
Immune System Diseases
Pathologic Processes
Lymphatic Diseases
Immunoproliferative Disorders
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Histiocytosis, Non-Langerhans-Cell
Eye Diseases, Hereditary
Eye Diseases
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents