Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

Chronic Granulomatous Disease Clinical Trial

Official title:

Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01652092
• Other study ID #: 2012OC055
• Secondary ID: MT2012-10C
• Status: Recruiting
• Phase: N/A
• Start date: September 4, 2012
• Est. completion date: December 2026

Study information

• Verified date: January 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Christen Ebens, MD
• Phone: 612-626-2778
• Email: ebens012[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Bare Lymphocyte Syndrome
• CD40 Ligand Deficiency
• Chediak-Higashi Syndrome
• Chronic Granulomatous Disease
• Common Variable Immunodeficiency
• Granulomatous Disease, Chronic
• Griscelli Syndrome
• Hemophagocytic Lymphohistiocytosis
• Histiocytosis
• Histiocytosis, Langerhans-Cell
• Hyper IgM Syndrome
• Immunologic Deficiency Syndromes
• Langerhan's Cell Histiocytosis
• Lymphohistiocytosis, Hemophagocytic
• Lymphoproliferative Disorders
• Omenn's Syndrome
• Primary Immunodeficiency Diseases
• Reticular Dysgenesis
• SCID
• Severe Combined Immunodeficiency
• Syndrome
• Wiskott-Aldrich Syndrome
• X-linked Lymphoproliferative Disease

Intervention

Drug:
• Alemtuzumab 0.3 mg
0.3 mg/kg intravenously (IV) on days -12 through -10
• Cyclophosphamide
cyclophosphamide 50 mg/kg IV on days -9 through -6
• Busulfan
busulfan 0.8 or 1.1 mg/kg IV on days -5 through -2

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)
• Melphalan
140 mg/m^2 IV on day -3
• Alemtuzumab 0.2 mg
0.2 mg/kg intravenously (IV) on days -14 through -10
• Busulfan
busulfan 0.8 or 1.1 mg/kg IV on days -9 through -6
• Fludarabine phosphate 30 mg
fludarabine 30 mg/m^2 IV on days -8 through -4
• MESNA
administered as per the standard institutional protocol.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Day 100
Secondary	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.	Day 100, 6 Months, 1 Year
Secondary	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.	Day 100
Secondary	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.	6 Months and 1 Year
Secondary	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.	6 Months
Secondary	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.	6 Months
Secondary	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.	6 Months