Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease

NCT00578643 | Completed Phase 2 Results DMC

• 1 other identifier: 14771-MUNCHR
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for patients with chronic granulomatous disease (CGD), which is a disorder of the immune system that puts them at risk for severe infections. CGD is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. This condition cannot presently be cured by standard treatment with drugs or surgery. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment, most patients with CGD will have chronic and recurrent infections. Transfusion of white blood cells may help overcome infection, but white cell transfusions lead to allergic reactions and fever and the benefit of transfusion lasts only a matter of hours. Ultimately, chronic infections can damage or injure the body organs. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs too. Infections may become resistant to antibiotic or antifungal treatment, and infections not responding to treatment can be deadly. It is now known that under specific conditions and with special treatment, blood stem cells (the cells that make blood) can be transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy sibling and who share the same immune type (HLA type) as the patient. Stem cell transplantation allows healthy or normal white cells from the stem cell donor to grow or develop in the patient's bone marrow. These healthy white cells can fight infection and prevent future infections for a patient with CGD. Patients on this study will receive stem cells from a related or unrelated donor. The donor will be closely matched to the patient's immune type but the donor is not a sibling. The reason this treatment is investigational is that we do not know the likelihood of benefit that the patient will receive. It is possible that they will have great benefit, like some of the patients who have been transplanted from a brother or sister. It is possible that the side-effects of treatment may be too severe so that the transplant won't work. The purpose of this research study is to evaluate whether or not patients with CGD treated with a stem cell transplant from a non-matched and/or non-related donor can have a good outcome from the procedure with an acceptable number of side-effects.

Conditions

Chronic Granulomatous Disease

Keywords

Stem Cell Transplant; Chronic Granulomatous Disease; Fludarabine; Busulfan; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Engraftment

  To estimate the engraftment rate for patients with CGD using busulfan, cyclophosphamide, fludarabine and alemtuzumab (Campath 1H) as conditioning therapy for SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors.

  28 days post transplant

Secondary Outcomes (3)

• Number of Patients That Have Complete Donor Chimerism After Transplant.

  120 days post transplant

• Number of Patients That Have Acute GVHD and Regimen Related Morbidity/Mortality Post Transplant.

  Assessed between day 0 and day 100 post transplant

• Number of Patients That Have Chronic GVHD and Regimen Related Morbidity/Mortality Post Transplant.

  Assessed between day 100 and day 365 post transplant

Study Arms (1)

Allogeneic unrelated transplant

EXPERIMENTAL

Conditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion.

Drug: Busulfan; Biological: Alemtuzumab; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Cyclosporine; Procedure: Stem Cell Infusion

Interventions

Busulfan DRUG

Days -9 through -6 1 mg/kg initially (based on weight)

Also known as: Busulfex

Allogeneic unrelated transplant

Alemtuzumab BIOLOGICAL

Day -5 through Day -2 Dose is based on weight: Less than 15 kg: 3 mg More than 15 kg to 30 kg: 5 mg More than 30 kg: 15 mg

Also known as: Campath

Allogeneic unrelated transplant

Cyclophosphamide DRUG

Days -5 through -2 50 mg/kg

Also known as: Cytoxan

Allogeneic unrelated transplant

Fludarabine DRUG

Day -5 through Day -2 30 mg/m\^2

Also known as: Fludara

Allogeneic unrelated transplant

Cyclosporine DRUG

Cyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours.

Also known as: Sandimmune

Allogeneic unrelated transplant

Stem Cell Infusion PROCEDURE

Stem Cell: Either bone marrow, cord blood, or peripheral blood stem cells may be used for stem cell transplantation. It is desired to infuse: for bone marrow, nucleated cells ≥ 4 X 10\^8/kg recipient weight; for cord blood ≥ 3 X 10\^7/kg nucleated cells; for peripheral blood stem cells ≥ 1 X 10\^/kg CD34+ cells.

Allogeneic unrelated transplant

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• CGD patients as documented by an abnormal NBT assay in a male patient and/or abnormal NADPH enzyme mutation confirmed by genetic analysis with abnormal NBT.
• Patients must not have an HLA genotype identical donor.
• Patients must have a 5/6 or 6/6 HLA-matched unrelated donor or a 5/6 or 6/6 HLA phenotype-matched related donor.
• Patients must have had at least one serious infection characteristic of those manifested in patients with CGD.
• Patients must not have active infection. An active infection may include the following: 1) clinical findings consistent with an infection such as fever, cavitary organ lesions, osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic imaging (two or more studies at least 1 month a part).
• No cumulative organ dysfunction that, in the estimation of the treating physicians, will diminish the patient's likelihood to survive this procedure.
• Negative pregnancy test for post-pubertal female patients.
• Echocardiogram shortening fraction \>/= 28%.
• DLCO 50% or greater predicted or FEV1 \>/= 50% predicted.

You may not qualify if:

• Active or uncontrolled infection (e.g. lung infection, cavitary organ lesions, osteomyelitis).
• Markedly elevated C reactive protein or sedimentation rate relative to patient's baseline.
• Invasive bone or bone marrow disease.
• Lack of potential hematologic blood product donors in the past (related to McLeod phenotype).

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Interventions

Busulfan; Alemtuzumab; Cyclophosphamide; fludarabine; fludarabine phosphate; Cyclosporine

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; 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; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Results Point of Contact

• Title: Robert Krance, MD
• Organization: Baylor College of Medicine

rakrance@txch.org

(832) 824-4661

Study Officials

• Robert Krance, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Hematology Oncology

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: March 1, 2004
• Primary Completion: July 31, 2017
• Study Completion: November 24, 2017
• Last Updated: November 9, 2018
• Results First Posted: November 9, 2018

Record last verified: 2018-10

Locations

US (1)