Chronic Granulomatous DiseasePhase 2NCT00006417
Modified Stem Cell Transplantation Procedure for Treating Chronic Granulomatous Disease
A Phase 2 study testing Stem cell transplantation in people with Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic granulomatous disease (CGD) in patients with active infection. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Granulomatous Disease
- What is being tested?
- Stem cell transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2000to Nov 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- PATIENT:
- Ages 1-55 years.
- DHR proven CGD: Includes gp91phox, p47phox, p22phox, and p67phox deficiency.
- Must have an active, life threatening non-viral infection that persists despite adequate and appropriate medical or surgical therapy (continued presence of pathogens on histology, culture positivity or continued radiographic evidence of infection). Patients with a progressive infectious process despite appropriate medical or surgical intervention may be considered for expedited enrollment into the study.
- HIV negative.
- No major organ dysfunction precluding transplantation.
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- HLA identical sibling or parent compatible at all 6 of the HLA A, B and DR antigens by molecular typing techniques.
- Left ventricular ejection fraction greater than 35% predicted.
- ECOG performance status of 0-3.
- DONOR:
- HLA identical sibling or parent donor.
- Fit to receive G-CSF and give peripheral blood stem cells (weight over 18kg, normal blood count, normotensive, no history of stroke, no history of severe heart disease).
- Female carriers of X-linked must have greater than 30% normal neutrophils.
- If donor is a sibling who is a minor, he/she is the oldest eligible sibling and no adults are eligible donors.
Who cannot join
- Pregnant patients or donors.
- Age greater than 55 years.
- ECOG performance status of 4 or more. Psychiatric disorder or mental deficiency of the patient or the donor sufficiently severe as to make compliance with PBSC transplantation treatment unlikely, and making informed consent impossible.
- Evidence of rapid deterioration due to progressive infection and/or organ damage.
- Left ventricular ejection fraction: less than 35% predicted.
- Creatinine Clearance less than 50. A maximum age adjusted serum creatinine will be used for patients who are unable to provide an accurate 24 hour urine collection.
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- Serum bilirubin greater 4 mg/dl, Transaminases greater than 4 times the upper limit of normal.
- HIV positive (donor or recipient). Donors who are positive for HBV, HCV or HTLV will be used at the discretion of the investigator.
- Malignant diseases liable to relapse or progress within 5 years.
- Donor who is unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of stroke, history of heart disease, thrombocytopenia, massive splenomegaly).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: HLA-Matched, Peripheral Blood Stem Cell Transplantation Using Low Intensity Conditioning to Treat Patients With Chronic Granulomatous Disease Who Are Actively Infected
This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic granulomatous disease (CGD) in patients with active infection. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Standard treatment with antibiotics, and sometimes surgery, is not always successful, and patients with persisting infections have a poor long-term prognosis.
Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets) can cure CGD. However, this procedure carries a significant risk of death, particularly in patients with active infection, because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells "see" patient's cells as "foreign" and mount an immune response to reject them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy and no radiation, a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD.
Read more
Patients with CGD between the ages of age 1 and 55 years old who have an active non-viral infection may be eligible for this study. They will have a medical history, physical examination and blood tests (including testing for adequacy of the genetic match with the donor). A bone marrow sample will be taken to evaluate disease status. This test, done under a local anesthetic, uses a special needle to draw out bone marrow from the hipbone. A central venous catheter (flexible plastic tube placed in a vein) will be put in place before treatment begins. It will be used to draw and transfuse blood, give medications, and infuse the donated stem cells.
Several days before the transplant procedure, patients will start low-dose chemotherapy with cyclophosphamide and fludarabine, two commonly used anti-cancer drugs. They will also be given anti-thymocyte globulin to prevent rejection of the donated cells. When this conditioning therapy is completed, the stem cells will be infused through the central line. Patients will be given cyclosporine 4 days before and 3 months after the stem cell transplant to help prevent rejection.
About 3 weeks after the transplant, patients will be discharged from the hospital. They will return for follow-up clinic visits weekly and then twice weekly for 3 months. These visits will include a symptom check, physical examination, and blood tests. Blood transfusions will be given if needed. Subsequent visits will be scheduled at 4, 6, 12, 18, 24, 30 and 36 months after the transplant, or more often if required, and then yearly.
Read the detailed description
Chronic Granulomatous Disease (CGD) is an inherited disorder of neutrophil function. Patients are profoundly immunocompromised and are plagued early in life with recurrent and life threatening infections. The prognosis for CGD patients whose infection persists despite appropriate medical and surgical intervention is extremely poor. Allogeneic stem cell transplantation can cure CGD however the mortality of this procedure is high for patients who are actively infected. Ongoing clinical trials at the NIH and elsewhere suggest that the use of non-myeloablative conditioning for allogeneic stem cell transplantation is safer and less toxic for patients who are free of infection at the time of transplant. The goal of this phase II study is to investigate the safety and efficacy of this novel approach to allogeneic stem cell transplantation for CGD patients who are actively infected. Following a preparative regimen designed to provide intense immunosuppression without myeloablation, patients will receive a peripheral blood stem cell graft from an HLA identical parent or sibling. Donor T-cells will be infused post-transplant if donor stem engraftment is unsatisfactory.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GvHD, infection status, immune reconstitution, and transplant related morbidity and mortality.
- Conditions
- Chronic Granulomatous Disease
- Being tested
- Stem cell transplantation
- Keywords
- Fludarabine, Non-Myeloablative BMT, Immunodeficiency, Neutrophils, Oxidase, Engraftment, Graft-versus-host Disease, Cyclophosphamide, Donor Apheresis, Peripheral Blood Stem Cells, Therapy
- Medical subject headings
- Granulomatous Disease, Chronic, Immunologic Deficiency Syndromes, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem cell transplantationProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2000 (estimated)
- Study startOct 2000
- Study completionNov 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Granulomatous DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 10 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006417
- Sponsor's protocol ID
- 010013
- Other IDs
- 01-I-0013
- Status last verified
- Nov 2004
- First submitted
- 24 Oct 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Kamani N, August CS, Campbell DE, Hassan NF, Douglas SD. Marrow transplantation in chronic granulomatous disease: an update, with 6-year follow-up. J Pediatr. 1988 Oct;113(4):697-700. doi: 10.1016/s0022-3476(88)80382-2. No abstract available.
PubMed 3050003Rappeport JM, Newburger PE, Goldblum RM, Goldman AS, Nathan DG, Parkman R. Allogeneic bone marrow transplantation for chronic granulomatous disease. J Pediatr. 1982 Dec;101(6):952-5. doi: 10.1016/s0022-3476(82)80017-6. No abstract available.
PubMed 6754900Kamani N, August CS, Douglas SD, Burkey E, Etzioni A, Lischner HW. Bone marrow transplantation in chronic granulomatous disease. J Pediatr. 1984 Jul;105(1):42-6. doi: 10.1016/s0022-3476(84)80354-6.
PubMed 6376746
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HLA-Matched, Peripheral Blood Stem Cell Transplantation Using Low Intensity Conditioning to Treat Patients With Chronic Granulomatous Disease Who Are Actively Infected
- ClinicalTrials.gov ID
- NCT00006417
- Acronym / sponsor ID
- 010013
- Conditions
- Chronic Granulomatous Disease
- Keywords
- Fludarabine, Non-Myeloablative BMT, Immunodeficiency, Neutrophils, Oxidase, Engraftment, Graft-versus-host Disease, Cyclophosphamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Oct 2000
- Study completion
- Nov 2004
- First posted
- 25 Oct 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic granulomatous disease (CGD) in patients with active infection. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Standard treatment with antibiotics, and sometimes surgery, is not always successful, and patients with persisting infections have a poor long-term prognosis.
Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets) can cure CGD. However, this procedure carries a significant risk of death, particularly in patients with active infection, because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells "see" patient's cells as "foreign" and mount an immune response to reject them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy and no radiation, a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD.
Patients with CGD between the ages of age 1 and 55 years old who have an active non-viral infection may be eligible for this study. They will have a medical history, physical examination and blood tests (including testing for adequacy of the genetic match with the donor). A bone marrow sample will be taken to evaluate disease status. This test, done under a local anesthetic, uses a special needle to draw out bone marrow from the hipbone. A central venous catheter (flexible plastic tube placed in a vein) will be put in place before treatment begins. It will be used to draw and transfuse blood, give medications, and infuse the donated stem cells.
Several days before the transplant procedure, patients will start low-dose chemotherapy with cyclophosphamide and fludarabine, two commonly used anti-cancer drugs. They will also be given anti-thymocyte globulin to prevent rejection of the donated cells. When this conditioning therapy is completed, the stem cells will be infused through the central line. Patients will be given cyclosporine 4 days before and 3 months after the stem cell transplant to help prevent rejection.
About 3 weeks after the transplant, patients will be discharged from the hospital. They will return for follow-up clinic visits weekly and then twice weekly for 3 months. These visits will include a symptom check, physical examination, and blood tests. Blood transfusions will be given if needed. Subsequent visits will be scheduled at 4, 6, 12, 18, 24, 30 and 36 months after the transplant, or more often if required, and then yearly.
Detailed description
Chronic Granulomatous Disease (CGD) is an inherited disorder of neutrophil function. Patients are profoundly immunocompromised and are plagued early in life with recurrent and life threatening infections. The prognosis for CGD patients whose infection persists despite appropriate medical and surgical intervention is extremely poor. Allogeneic stem cell transplantation can cure CGD however the mortality of this procedure is high for patients who are actively infected. Ongoing clinical trials at the NIH and elsewhere suggest that the use of non-myeloablative conditioning for allogeneic stem cell transplantation is safer and less toxic for patients who are free of infection at the time of transplant. The goal of this phase II study is to investigate the safety and efficacy of this novel approach to allogeneic stem cell transplantation for CGD patients who are actively infected. Following a preparative regimen designed to provide intense immunosuppression without myeloablation, patients will receive a peripheral blood stem cell graft from an HLA identical parent or sibling. Donor T-cells will be infused post-transplant if donor stem engraftment is unsatisfactory.
The end points of this study are engraftment, degree of donor-host chimerism, incidence of acute and chronic GvHD, infection status, immune reconstitution, and transplant related morbidity and mortality.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Ages 1-55 years.
- DHR proven CGD: Includes gp91phox, p47phox, p22phox, and p67phox deficiency.
- Must have an active, life threatening non-viral infection that persists despite adequate and appropriate medical or surgical therapy (continued presence of pathogens on histology, culture positivity or continued radiographic evidence of infection). Patients with a progressive infectious process despite appropriate medical or surgical intervention may be considered for expedited enrollment into the study.
- HIV negative.
- No major organ dysfunction precluding transplantation.
Key exclusion criteria (10 listed)
- Pregnant patients or donors.
- Age greater than 55 years.
- ECOG performance status of 4 or more. Psychiatric disorder or mental deficiency of the patient or the donor sufficiently severe as to make compliance with PBSC transplantation treatment unlikely, and making informed consent impossible.
- Evidence of rapid deterioration due to progressive infection and/or organ damage.
- Left ventricular ejection fraction: less than 35% predicted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stem cell transplantation | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 3050003Kamani N, August CS, Campbell DE, Hassan NF, Douglas SD. Marrow transplantation in chronic granulomatous disease: an update, with 6-year follow-up. J Pediatr. 1988 Oct;113(4):697-700. doi: 10.1016/s0022-3476(88)80382-2. No abstract available.
- Background: PubMed 6754900Rappeport JM, Newburger PE, Goldblum RM, Goldman AS, Nathan DG, Parkman R. Allogeneic bone marrow transplantation for chronic granulomatous disease. J Pediatr. 1982 Dec;101(6):952-5. doi: 10.1016/s0022-3476(82)80017-6. No abstract available.
- Background: PubMed 6376746Kamani N, August CS, Douglas SD, Burkey E, Etzioni A, Lischner HW. Bone marrow transplantation in chronic granulomatous disease. J Pediatr. 1984 Jul;105(1):42-6. doi: 10.1016/s0022-3476(84)80354-6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stem cell transplantation in people with Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006417, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.