search
Back to results

Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

Primary Purpose

SCID, Omenn's Syndrome, Reticular Dysgenesis

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Alemtuzumab 0.3 mg
Cyclophosphamide
Busulfan
Stem Cell Transplantation
Fludarabine phosphate 40 mg
Melphalan
Alemtuzumab 0.2 mg
Busulfan
Fludarabine phosphate 30 mg
MESNA
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for SCID focused on measuring immunodeficiency disorder, histiocytic disorder

Eligibility Criteria

undefined - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center, University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

Arm A: Fully Myeloablative regimen

Arm B: Reduced Toxicity Ablative Regimen

Arm C: Reduced Intensity Conditioning

Arm D: No Preparative Regimen

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Neutrophil Engraftment
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

Incidence of Graft Failure
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
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
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
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
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
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
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.

Full Information

First Posted
July 25, 2012
Last Updated
January 25, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
search

1. Study Identification

Unique Protocol Identification Number
NCT01652092
Brief Title
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Official Title
Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 4, 2012 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
immunodeficiency disorder, histiocytic disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Fully Myeloablative regimen
Arm Type
Other
Arm Description
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.
Arm Title
Arm B: Reduced Toxicity Ablative Regimen
Arm Type
Other
Arm Description
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.
Arm Title
Arm C: Reduced Intensity Conditioning
Arm Type
Other
Arm Description
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.
Arm Title
Arm D: No Preparative Regimen
Arm Type
Other
Arm Description
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 Type
Drug
Intervention Name(s)
Alemtuzumab 0.3 mg
Other Intervention Name(s)
Campath-1H
Intervention Description
0.3 mg/kg intravenously (IV) on days -12 through -10
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
cyclophosphamide 50 mg/kg IV on days -9 through -6
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Myerlan
Intervention Description
busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2
Intervention Type
Biological
Intervention Name(s)
Stem Cell Transplantation
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine phosphate 40 mg
Other Intervention Name(s)
Fludara
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
140 mg/m^2 IV on day -3
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab 0.2 mg
Other Intervention Name(s)
Campath 1-H
Intervention Description
0.2 mg/kg intravenously (IV) on days -14 through -10
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Myerlan
Intervention Description
busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6
Intervention Type
Drug
Intervention Name(s)
Fludarabine phosphate 30 mg
Other Intervention Name(s)
Fludara
Intervention Description
fludarabine 30 mg/m^2 IV on days -8 through -4
Intervention Type
Drug
Intervention Name(s)
MESNA
Other Intervention Name(s)
mercaptoethane sulfonate Na (Na being the symbol for sodium), Mesnex
Intervention Description
administered as per the standard institutional protocol.
Primary Outcome Measure Information:
Title
Neutrophil Engraftment
Description
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.
Time Frame
Day 42
Secondary Outcome Measure Information:
Title
Incidence of Graft Failure
Description
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.
Time Frame
Day 100
Title
Incidence of Chimerism
Description
a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease.
Time Frame
Day 100, 6 Months, 1 Year
Title
Incidence of Acute Graft-Versus-Host Disease
Description
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame
Day 100
Title
Incidence of Chronic Graft-Versus-Host Disease
Description
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame
6 Months and 1 Year
Title
Incidence of Transplant-Related Mortality
Description
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame
6 Months
Title
Disease-Free Survival
Description
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.
Time Frame
6 Months
Title
Overall Survival
Description
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.
Time Frame
6 Months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christen Ebens, MD
Phone
612-626-2778
Email
ebens012@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christen Ebens, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christen Ebens, MD
Phone
612-626-2778
Email
ebens012@umn.edu
First Name & Middle Initial & Last Name & Degree
Christen Ebens, MD

12. IPD Sharing Statement

Learn more about this trial

Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

We'll reach out to this number within 24 hrs