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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 7, 2020
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE July 25, 2012
First Posted Date  ICMJE July 27, 2012
Last Update Posted Date January 7, 2020
Study Start Date  ICMJE September 4, 2012
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2012)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Official Title  ICMJE Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Brief Summary This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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: 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: 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: Busulfan
    busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6
    Other Name: Myerlan
  • Drug: Fludarabine phosphate 30 mg
    fludarabine 30 mg/m^2 IV on days -8 through -4
    Other Name: Fludara
  • Drug: MESNA
    administered as per the standard institutional protocol.
    Other Names:
    • mercaptoethane sulfonate Na (Na being the symbol for sodium)
    • Mesnex
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Alemtuzumab 0.3 mg
    • Drug: Cyclophosphamide
    • Drug: Busulfan
    • Biological: Stem Cell Transplantation
    • Drug: MESNA
  • 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.
    Interventions:
    • Drug: Alemtuzumab 0.3 mg
    • Biological: Stem Cell Transplantation
    • Drug: Fludarabine phosphate 40 mg
    • Drug: Busulfan
  • 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.
    Interventions:
    • Biological: Stem Cell Transplantation
    • Drug: Melphalan
    • Drug: Alemtuzumab 0.2 mg
    • Drug: Fludarabine phosphate 30 mg
  • 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.
    Intervention: Biological: Stem Cell Transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 26, 2012)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Angela R. Smith, M.D. 612-626-2778 smith719@umn.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01652092
Other Study ID Numbers  ICMJE 2012OC055
MT2012-10C ( Other Identifier: Blood and Marrow Transplantation Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Angela R. Smith, M.D. Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP