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

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ClinicalTrials.gov Identifier: NCT00578643
Recruitment Status : Active, not recruiting
First Posted : December 21, 2007
Last Update Posted : June 15, 2018
Sponsor:
Collaborator:
Texas Children's Hospital
Information provided by (Responsible Party):
Robert Krance, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Chronic Granulomatous Disease Drug: Busulfan Biological: Alemtuzumab Drug: Cyclophosphamide Drug: Fludarabine Drug: Cyclosporine Procedure: Stem Cell Infusion Phase 2

Detailed Description:

In order to transplant stem cells we will need to give the patient drugs or high-dose chemotherapy to kill or destroy most of the blood forming and immune cells in the bone marrow. This is necessary to allow the donor stem cells to live and grow (engraft) in the bone marrow space. After the drug treatment is completed, the patient will be given the stem cells from the donor. The drug treatment is as follows:

Day -9 Busulfan

Day -8 Busulfan

Day -7 Busulfan

Day -6 Busulfan

Day -5 Alemtuzumab, Fludarabine, Cyclophosphamide

Day -4 Alemtuzumab, Fludarabine, Cyclophosphamide

Day -3 Alemtuzumab, Fludarabine, Cyclophosphamide

Day -2 Alemtuzumab, Fludarabine, Cyclosporine, Cyclophosphamide

Day -1 REST

Day 0 Stem cell infusion

The day after the chemotherapy treatment is completed, the patient will receive the healthy stem cells by vein, like a blood transfusion. Once in the bloodstream, the marrow cells will go to the bone marrow and grow.

It is also possible that if the marrow takes, it will cause a disease known as graft-versus-host disease (GVHD). To prevent GVHD, we will give the patient cyclosporine and Methotrexate. Methotrexate will be administered on Days 1, 3, 6 and 11 after the transplant. The cyclosporine therapy will continue for a longer period of time, however if the patient does not develop GVHD, it will be discontinued by 6 months after the stem cell transplant.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
Study Start Date : March 2004
Actual Primary Completion Date : July 31, 2017
Estimated Study Completion Date : July 31, 2018


Arm Intervention/treatment
Experimental: Allogeneic unrelated transplant
Conditioning from Day -9 to Day -1. Stem cells given on Day 0. Busulfan, alemtuzumab, cyclophosphamide, fludarabine, cyclosporine, stem cell infusion.
Drug: Busulfan

Days -9 through -6

1 mg/kg initially (based on weight)

Other Name: Busulfex

Biological: Alemtuzumab

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

Other Name: Campath

Drug: Cyclophosphamide

Days -5 through -2

50 mg/kg

Other Name: Cytoxan

Drug: Fludarabine

Day -5 through Day -2

30 mg/m^2

Other Name: Fludara

Drug: Cyclosporine
Cyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours.
Other Name: Sandimmune

Procedure: Stem Cell Infusion
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.




Primary Outcome Measures :
  1. Number of patients that have engraftment after transplant. [ Time Frame: 28 days post transplant ]
    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.


Secondary Outcome Measures :
  1. Number of patients that have complete donor chimerism after transplant. [ Time Frame: 120 days post transplant ]
    To estimate the likelihood of complete donor chimerism 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.

  2. Number of patients that have acute GVHD and regimen related morbidity/mortality post transplant. [ Time Frame: Assessed between day 0 and day 100 post transplant ]
    To estimate the risk for acute GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.

  3. Number of patients that have chronic GVHD and regimen related morbidity/mortality post transplant. [ Time Frame: Assessed between day 100 and day 365 post transplant ]
    To estimate the risk for chronic GVHD and regimen related morbidity/mortality for patients with CGD following stem cell transplant from 5/6 or 6/6 HLA matched unrelated or 5/6 or 6/6 HLA phenotype matched related donors.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00578643


Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Robert Krance, MD Baylor College of Medicine

Responsible Party: Robert Krance, Professor, Hematology Oncology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00578643     History of Changes
Other Study ID Numbers: 14771-MUNCHR
First Posted: December 21, 2007    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: August 2017

Keywords provided by Robert Krance, Baylor College of Medicine:
Stem Cell Transplant
Chronic Granulomatous Disease
Fludarabine
Busulfan
Cyclophosphamide

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Granuloma
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Cyclosporins
Cyclosporine
Busulfan
Fludarabine
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites