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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Baylor College of Medicine
Sponsor:
Collaborator:
Texas Children's Hospital
Information provided by (Responsible Party):
Robert Krance, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00578643
First received: December 19, 2007
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

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. The course over time of CGD may differ in severity among patients, but those children who develop severe infection at a young age are most likely to have a more severe clinical course. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment with these medications, most patients with CGD will have chronic and recurrent infections. Transfusion of healthy or normal 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 such as the lung, liver, or bone. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs such as the kidney. 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 transferred or transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy brother or sister 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 making the donor's white cells. 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 an unrelated donor. The donor will be closely matched to the patients immune type but the donor is not a brother or sister. This type of transplantation has been done only a few times for patients with CGD, although this type of transplant is commonly done for other reasons, e.g. leukemia. 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 Intervention Phase
Chronic Granulomatous Disease
Drug: Busulfan
Biological: Alemtuzumab
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Cyclosporine
Procedure: Stem Cell Infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HLA Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of patients that have engraftment after transplant. [ Time Frame: 120 days ] [ Designated as safety issue: No ]
    To estimate the engraftment rate and 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.


Secondary Outcome Measures:
  • Estimating the risk for acute and chronic GVHD and regimen related morbidity/mortality for patients with CGD following SCT from 5/6 or 6/6 HLA-matched unrelated or 5/6 or 6/6 HLA phenotype-matched related donors. [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
  • Examining the potential for reversal of organ toxicity (e.g. lung, liver, intestine) following engraftment and stable normal neutrophil function. [ Time Frame: 120 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: February 2004
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Genders Eligible for Study:   Both
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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578643

Contacts
Contact: Robert Krance, MD 832-824-4661 rakrance@txch.org
Contact: Marlen Dinu 832-824-4881 mxdinu@txch.org

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Robert Krance, MD    832-824-4661    rakrance@txch.org   
Contact: Marlen Dinu    832-824-4881    mxdinu@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Robert Krance, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Robert Krance, Professor, Hematology Oncology, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00578643     History of Changes
Other Study ID Numbers: 14771-MUNCHR
Study First Received: December 19, 2007
Last Updated: September 9, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by 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
Busulfan
Fludarabine phosphate
Cyclosporins
Cyclosporine
Alemtuzumab
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 19, 2014