Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

NCT ID: NCT01652092

Last Updated: 2026-01-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-04
• Study Completion Date: 2026-12-31

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

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Alemtuzumab 0.3 mg

Intervention Type: DRUG

0.3 mg/kg intravenously (IV) on days -12 through -10

Cyclophosphamide

Intervention Type: DRUG

cyclophosphamide 50 mg/kg IV on days -9 through -6

Busulfan

Intervention Type: DRUG

busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2

Stem Cell Transplantation

Intervention Type: BIOLOGICAL

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.

MESNA

Intervention Type: DRUG

administered as per the standard institutional protocol.

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.

Group Type: OTHER

Alemtuzumab 0.3 mg

Intervention Type: DRUG

0.3 mg/kg intravenously (IV) on days -12 through -10

Stem Cell Transplantation

Intervention Type: BIOLOGICAL

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.

Fludarabine phosphate 40 mg

Intervention Type: DRUG

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)

Busulfan

Intervention Type: DRUG

busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6

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.

Group Type: OTHER

Stem Cell Transplantation

Intervention Type: BIOLOGICAL

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.

Melphalan

Intervention Type: DRUG

140 mg/m\^2 IV on day -3

Alemtuzumab 0.2 mg

Intervention Type: DRUG

0.2 mg/kg intravenously (IV) on days -14 through -10

Fludarabine phosphate 30 mg

Intervention Type: DRUG

fludarabine 30 mg/m\^2 IV on days -8 through -4

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.

Group Type: OTHER

Stem Cell Transplantation

Intervention Type: BIOLOGICAL

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.

Interventions

Alemtuzumab 0.3 mg

0.3 mg/kg intravenously (IV) on days -12 through -10

Intervention Type: DRUG

Cyclophosphamide

cyclophosphamide 50 mg/kg IV on days -9 through -6

Intervention Type: DRUG

Busulfan

busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

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)

Intervention Type: DRUG

Melphalan

140 mg/m\^2 IV on day -3

Intervention Type: DRUG

Alemtuzumab 0.2 mg

0.2 mg/kg intravenously (IV) on days -14 through -10

Intervention Type: DRUG

Busulfan

busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6

Intervention Type: DRUG

Fludarabine phosphate 30 mg

fludarabine 30 mg/m\^2 IV on days -8 through -4

Intervention Type: DRUG

MESNA

administered as per the standard institutional protocol.

Intervention Type: DRUG

Other Intervention Names

Campath-1H; Cytoxan; Myerlan; Fludara; Alkeran; Campath 1-H; Myerlan; Fludara; mercaptoethane sulfonate Na (Na being the symbol for sodium); Mesnex

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

• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christen Ebens, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

MT2012-10C

Identifier Type: OTHER

Identifier Source: secondary_id

2012OC055

Identifier Type: -

Identifier Source: org_study_id