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Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01652092
Recruitment Status : Recruiting
First Posted : July 27, 2012
Last Update Posted : January 26, 2023
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Description
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Brief Summary:
This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.

Condition or disease Intervention/treatment Phase
SCID Omenn's Syndrome Reticular Dysgenesis Wiskott-Aldrich Syndrome Bare Lymphocyte Syndrome Common Variable Immunodeficiency Chronic Granulomatous Disease CD40 Ligand Deficiency Hyper IgM Syndrome X-linked Lymphoproliferative Disease Hemophagocytic Lymphohistiocytosis Griscelli Syndrome Chediak-Higashi Syndrome Langerhan's Cell Histiocytosis Drug: Alemtuzumab 0.3 mg Drug: Cyclophosphamide Drug: Busulfan Biological: Stem Cell Transplantation Drug: Fludarabine phosphate 40 mg Drug: Melphalan Drug: Alemtuzumab 0.2 mg Drug: Fludarabine phosphate 30 mg Drug: MESNA Not Applicable

Detailed Description:

Based on diagnosis and clinical history, a determination of the most appropriate regimen will be made based on the following prep plans:

Arm A: Fully Myeloablative Preparative Regimen, Arm B: Reduced Toxicity Ablative Preparative Regimen, Arm C: Reduced Intensity Conditioning, Arm D: No Preparative Regimen

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Actual Study Start Date : September 4, 2012
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Arm A: Fully Myeloablative regimen
For use in patients with diseases including Wiskott-Aldrich syndrome, MHC Class II deficiency, hypomorphic SCID, etc. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, cyclophosphamide 50 mg/kg IV plus MESNA on days -9 through -6, busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2 and stem cell infusion on day 0.
 Drug: Alemtuzumab 0.3 mg
0.3 mg/kg intravenously (IV) on days -12 through -10
Other Name: Campath-1H

Drug: Cyclophosphamide
cyclophosphamide 50 mg/kg IV on days -9 through -6
Other Name: Cytoxan

Drug: Busulfan
busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2
Other Name: Myerlan

Biological: Stem Cell Transplantation

Unrelated donor bone marrow will be collected in the usual manner using established parameters determined by the National Marrow Donor Program. A minimum of 3 x 10^8 nucleated cells/kg recipient weight will be collected with a goal of ≥ 5 x 10^8 nucleated cells/kg recipient weight.

Umbilical cord blood selection will be per the current University of Minnesota Cord Blood Unit Selection algorithm. One or two units may be used to obtain the minimum cell dose. One of the UCB units selected for transplantation must contain ≥ 3.5 x 10^7 nucleated cells/kg recipient weight based on cell numbers at time of cryopreservation, and the total combined cell dose of both units must be > 5.0 x 10^7 nucleated cells/kg.


Drug: MESNA
administered as per the standard institutional protocol.
Other Names:
  • mercaptoethane sulfonate Na (Na being the symbol for sodium)
  • Mesnex
Arm B: Reduced Toxicity Ablative Regimen
For use in patients with diseases including SCID, CGD, CHS and other CID. Receives Alemtuzumab 0.3 mg/kg intravenously (IV) on days -12 through -10, busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6, fludarabine phosphate 40 mg/m^2 IV on days -5 through -2 and stem cell infusion on day 0.
 Drug: Alemtuzumab 0.3 mg
0.3 mg/kg intravenously (IV) on days -12 through -10
Other Name: Campath-1H

Biological: Stem Cell Transplantation

Unrelated donor bone marrow will be collected in the usual manner using established parameters determined by the National Marrow Donor Program. A minimum of 3 x 10^8 nucleated cells/kg recipient weight will be collected with a goal of ≥ 5 x 10^8 nucleated cells/kg recipient weight.

Umbilical cord blood selection will be per the current University of Minnesota Cord Blood Unit Selection algorithm. One or two units may be used to obtain the minimum cell dose. One of the UCB units selected for transplantation must contain ≥ 3.5 x 10^7 nucleated cells/kg recipient weight based on cell numbers at time of cryopreservation, and the total combined cell dose of both units must be > 5.0 x 10^7 nucleated cells/kg.


Drug: Fludarabine phosphate 40 mg
40 mg/m^2 IV on days -5 through -2 (for children < 6 months and/or < 10 kg weight dose at 1.33 mg/kg)
Other Name: Fludara

Drug: Busulfan
busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6
Other Name: Myerlan
Arm C: Reduced Intensity Conditioning
For use in patients with diseases including HLH. Receives Alemtuzumab 0.2 mg/kg intravenously (IV) on days -14 through -10, fludarabine phosphate 30 mg/m^2 IV on days -8 through -4, melphalan 140 mg/m^2 IV on day -3 and stem cell infusion on day 0.
 Biological: Stem Cell Transplantation

Unrelated donor bone marrow will be collected in the usual manner using established parameters determined by the National Marrow Donor Program. A minimum of 3 x 10^8 nucleated cells/kg recipient weight will be collected with a goal of ≥ 5 x 10^8 nucleated cells/kg recipient weight.

Umbilical cord blood selection will be per the current University of Minnesota Cord Blood Unit Selection algorithm. One or two units may be used to obtain the minimum cell dose. One of the UCB units selected for transplantation must contain ≥ 3.5 x 10^7 nucleated cells/kg recipient weight based on cell numbers at time of cryopreservation, and the total combined cell dose of both units must be > 5.0 x 10^7 nucleated cells/kg.


Drug: Melphalan
140 mg/m^2 IV on day -3
Other Name: Alkeran

Drug: Alemtuzumab 0.2 mg
0.2 mg/kg intravenously (IV) on days -14 through -10
Other Name: Campath 1-H

Drug: Fludarabine phosphate 30 mg
fludarabine 30 mg/m^2 IV on days -8 through -4
Other Name: Fludara
Arm D: No Preparative Regimen
For use in patients with complete SCID phenotype with no evidence of maternal engraftment or residual immune function who will be receiving their stem cell transplantation from a genotypically matched donor.
 Biological: Stem Cell Transplantation

Unrelated donor bone marrow will be collected in the usual manner using established parameters determined by the National Marrow Donor Program. A minimum of 3 x 10^8 nucleated cells/kg recipient weight will be collected with a goal of ≥ 5 x 10^8 nucleated cells/kg recipient weight.

Umbilical cord blood selection will be per the current University of Minnesota Cord Blood Unit Selection algorithm. One or two units may be used to obtain the minimum cell dose. One of the UCB units selected for transplantation must contain ≥ 3.5 x 10^7 nucleated cells/kg recipient weight based on cell numbers at time of cryopreservation, and the total combined cell dose of both units must be > 5.0 x 10^7 nucleated cells/kg.


Outcome Measures
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Primary Outcome Measures :
  1. Neutrophil Engraftment [ Time Frame: Day 42 ]
    Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.


Secondary Outcome Measures :
  1. Incidence of Graft Failure [ Time Frame: Day 100 ]
    Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.

  2. Incidence of Chimerism [ Time Frame: Day 100, 6 Months, 1 Year ]
    a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease.

  3. Incidence of Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

  4. Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: 6 Months and 1 Year ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.

  5. Incidence of Transplant-Related Mortality [ Time Frame: 6 Months ]
    In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.

  6. Disease-Free Survival [ Time Frame: 6 Months ]
    the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

  7. Overall Survival [ Time Frame: 6 Months ]
    Overall survival will be defined as time from enrollment to date of death or censored at the date of last documented contact for patients still alive.


Eligibility Criteria
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Ages Eligible for Study:   up to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of immunodeficiency or histiocytic disorder including the following:

    • Severe combined immunodeficiency (SCID - all variants)
    • Second bone marrow transplant (BMT) for SCID (after graft rejection)
    • Omenn's Syndrome
    • Reticular dysgenesis
    • Wiskott-Aldrich syndrome
    • Major histocompatibility complex (MHC) Class II deficiency (bare lymphocyte syndrome)
    • Hyper IgM Syndrome (CD40 Ligand Deficiency)
    • Common variable immunodeficiency (CVID) with severe phenotype
    • Chronic Granulomatous Disease (CGD)
    • Other severe Combined Immune Deficiencies (CID)
    • Hemophagocytic Lymphohistiocytosis (HLH)
    • X-linked Lymphoproliferative Disease (XLP)
    • Chediak-Higashi Syndrome (CHS)
    • Griscelli Syndrome
    • Langerhans Cell Histiocytosis (LCH)

  • Acceptable stem cell sources include:

    • HLA identical or 1 antigen matched sibling donor eligible to donate bone marrow
    • HLA identical or up to a 1 antigen mismatched unrelated BM donor
    • Sibling donor cord blood with acceptable HLA match and cell dose as per current institutional standards
    • Single unrelated umbilical cord blood unit with 0-2 antigen mismatch and minimum cell dose of >5 x 10^7 nucleated cells/kg as per current institutional guidelines

    • Double unrelated umbilical cord blood units that are:

      • up to 2 antigen mismatched to the patient
      • up to 2 antigen mismatched to each other
      • minimum cell dose of at least one single unit must be ≥ 3.5 x 10^7 nucleated cells/kg
      • combined dose of both units must provide a total cell dose of ≥ 5 x 10^7 nucleated cells/kg
  • Age: 0 to 50 years
  • Adequate organ function and performance status.

Exclusion Criteria

  • pregnant or breastfeeding
  • active, uncontrolled infection and/or HIV positive
  • acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT01652092


Contacts
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Contact: Christen Ebens, MD 612-626-2778 ebens012@umn.edu

Locations
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United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Christen Ebens, MD    612-626-2778    ebens012@umn.edu   
Principal Investigator: Christen Ebens, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Christen Ebens, MD Masonic Cancer Center, University of Minnesota
More Information
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01652092    
Other Study ID Numbers: 2012OC055
MT2012-10C ( Other Identifier: Blood and Marrow Transplantation Program )
First Posted: July 27, 2012    Key Record Dates
Last Update Posted: January 26, 2023
Last Verified: January 2023
Keywords provided by Masonic Cancer Center, University of Minnesota:
immunodeficiency disorder
histiocytic disorder
Additional relevant MeSH terms:
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Histiocytosis, Langerhans-Cell
Chediak-Higashi Syndrome
Histiocytosis
Granulomatous Disease, Chronic
Lymphohistiocytosis, Hemophagocytic
Lymphoproliferative Disorders
Wiskott-Aldrich Syndrome
Hyper-IgM Immunodeficiency Syndrome
Hyper-IgM Immunodeficiency Syndrome, Type 1
Primary Immunodeficiency Diseases
Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Common Variable Immunodeficiency
Syndrome
Disease
 Pathologic Processes
Immune System Diseases
Lymphatic Diseases
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Chronic Disease
Disease Attributes
Histiocytosis, Non-Langerhans-Cell
Immunoproliferative Disorders
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hemorrhagic Disorders