Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

NCT01652092 | Active Not Recruiting DMC

• 2 other identifiers: 2012OC055MT2012-10C
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

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

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

Keywords

immunodeficiency disorder; histiocytic disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 42

Secondary Outcomes (7)

• Incidence of Graft Failure

  Day 100

• Incidence of Chimerism

  Day 100, 6 Months, 1 Year

• Incidence of Acute Graft-Versus-Host Disease

  Day 100

• Incidence of Chronic Graft-Versus-Host Disease

  6 Months and 1 Year

• Incidence of Transplant-Related Mortality

  6 Months

Study Arms (4)

Arm A: Fully Myeloablative regimen

OTHER

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; Drug: Cyclophosphamide; Drug: Busulfan; Biological: Stem Cell Transplantation; Drug: MESNA

Arm B: Reduced Toxicity Ablative Regimen

OTHER

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; Biological: Stem Cell Transplantation; Drug: Fludarabine phosphate 40 mg; Drug: Busulfan

Arm C: Reduced Intensity Conditioning

OTHER

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; Drug: Melphalan; Drug: Alemtuzumab 0.2 mg; Drug: Fludarabine phosphate 30 mg

Arm D: No Preparative Regimen

OTHER

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

Interventions

Alemtuzumab 0.3 mg DRUG

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

Also known as: Campath-1H

Arm A: Fully Myeloablative regimen; Arm B: Reduced Toxicity Ablative Regimen

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Arm A: Fully Myeloablative regimen

Busulfan DRUG

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

Also known as: Myerlan

Arm A: Fully Myeloablative regimen

Stem Cell Transplantation 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.

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

Fludarabine phosphate 40 mg 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)

Also known as: Fludara

Arm B: Reduced Toxicity Ablative Regimen

Melphalan DRUG

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

Also known as: Alkeran

Arm C: Reduced Intensity Conditioning

Alemtuzumab 0.2 mg DRUG

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

Also known as: Campath 1-H

Arm C: Reduced Intensity Conditioning

MESNA DRUG

administered as per the standard institutional protocol.

Also known as: mercaptoethane sulfonate Na (Na being the symbol for sodium), Mesnex

Arm A: Fully Myeloablative regimen

Fludarabine phosphate 30 mg DRUG

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

Also known as: Fludara

Arm C: Reduced Intensity Conditioning

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• pregnant or breastfeeding
• active, uncontrolled infection and/or HIV positive
• acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Reticular dysgenesis; Wiskott-Aldrich Syndrome; Common Variable Immunodeficiency; Granulomatous Disease, Chronic; Hyper-IgM Immunodeficiency Syndrome; Lymphoproliferative Disorders; Lymphohistiocytosis, Hemophagocytic; Chediak-Higashi Syndrome; Histiocytosis, Langerhans-Cell; Immunologic Deficiency Syndromes

Interventions

Alemtuzumab; Cyclophosphamide; Busulfan; Stem Cell Transplantation; fludarabine phosphate; Melphalan; Mesna; Sodium

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immune System Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, X-Linked; Phagocyte Bactericidal Dysfunction; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Dysgammaglobulinemia; Blood Protein Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Albinism; Eye Diseases, Hereditary; Eye Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Sulfhydryl Compounds; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Christen Ebens, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2012
• First Posted: July 27, 2012
• Study Start: September 4, 2012
• Primary Completion: December 30, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

US (1)