Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

University of Minnesota (UMN)

Status: Active, not recruiting

Conditions: CD40 Ligand Deficiency; Griscelli Syndrome; Bare Lymphocyte Syndrome; Chediak-Higashi Syndrome; Omenn's Syndrome; SCID; Reticular Dysgenesis; Hyper IgM Syndrome; Wiskott-Aldrich Syndrome; Hemophagocytic Lymphohistiocytosis; Chronic Granulomatous Disease; Common Variable Immunodeficiency; X-linked Lymphoproliferative Disease; Langerhan's Cell Histiocytosis

Treatments: Drug: Alemtuzumab 0.3 mg; Drug: Cyclophosphamide; Drug: Alemtuzumab 0.2 mg; Drug: Fludarabine phosphate 40 mg; Drug: Busulfan; Biological: Stem Cell Transplantation; Drug: MESNA; Drug: Melphalan; Drug: Fludarabine phosphate 30 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT01652092

2012OC055

MT2012-10C (Other Identifier)

Details and patient eligibility

About

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

Full 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

Enrollment: 57 patients

Sex: All

Ages: Under 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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57 participants in 4 patient groups

Arm A: Fully Myeloablative regimen

Other group

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.

Treatment:

Drug: MESNA

Biological: Stem Cell Transplantation

Drug: Busulfan

Drug: Busulfan

Drug: Cyclophosphamide

Drug: Alemtuzumab 0.3 mg

Arm B: Reduced Toxicity Ablative Regimen

Other group

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.

Treatment:

Biological: Stem Cell Transplantation

Drug: Busulfan

Drug: Fludarabine phosphate 40 mg

Drug: Busulfan

Drug: Alemtuzumab 0.3 mg

Arm C: Reduced Intensity Conditioning

Other group

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.

Treatment:

Drug: Fludarabine phosphate 30 mg

Drug: Melphalan

Biological: Stem Cell Transplantation

Drug: Alemtuzumab 0.2 mg

Arm D: No Preparative Regimen

Other group

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.

Treatment:

Biological: Stem Cell Transplantation