Leukocyte-Adhesion Deficiency SyndromePhase 2NCT00031005
Stem Cell Transplantation to Treat Leukocyte Adhesion Deficiency
A Phase 2 study testing modified stem cell transplant in people with Leukocyte-Adhesion Deficiency Syndrome, 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 modified stem cell transplant procedure for treating leukocyte adhesion deficiency (LAD). LAD is an inherited blood disorder of leukocytes (infection-fighting white blood cells) that leaves patients vulnerable to life-threatening infections. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukocyte-Adhesion Deficiency Syndrome
- What is being tested?
- modified stem cell transplant
- Type of treatment
- Surgery or procedure
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2002to Feb 2003
- 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
- Minimum weight of 12 kg.
- Disease criteria: LAD: less than 20% expression of CD18 (as measured by fluorescence intensity compared to controls) on peripheral leukocytes by flow cytometry and either: a) clinical history of 2 severe infections requiring intravenous anti-bacterial or anti-fungal treatment OR b) history of life-threatening non-healing skin lesions.
- Free of active infection. Patients with non-healing skin lesions may be enrolled after superinfection has been contained.
- Patients with consenting HLA-matched related donors that meet donor selection criteria.
- Patients with adequate organ function as measured by:
- Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be greater than 40%;
Show all 11Show fewer
- Hepatic: SGOT within 4x normal range and total bilirubin less than 4 mg/dl;
- Renal: Creatinine clearance greater than or equal to 50 ml/min/1.73m(2);
- Pulmonary: DLCO (diffusion capacity) and FEV1 greater than 45% of predicted (corrected for hemoglobin). Minors in whom pulmonary function tests are not possible will be evaluated for significant pulmonary dysfunction by a pulmonary consultant.
- Written informed consent/assent conforming to institutional guidelines obtained from patient and parent.
- Absence of co-existing medical problems that would significantly increase the risk of the transplant procedure in the judgment of the principal investigator.
Who cannot join
- Female patients who are pregnant or breast-feeding.
- ECOG performance status of 2 or less or greater than 50% on the Lansky scale for ages 0-10 .
- Seropositivity for HIV.
- Evidence of rapid deterioration due to progressive infection and/or organ damage.
- Malignant diseases liable to relapse or progress within 5 years.
- DONOR SELECTION:
Show all 11Show fewer
- Donors must be fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease, greater than 12 kg).
- Related to the patient and HLA-phenotypically identical with the patient for HLA-A, B and DRB1 alleles. Matching assessed minimally by serology for Class I and DNA typing for Class II antigens.
- Peripheral blood cells expressing normal levels of CD18.
- If donor is a sibling who is a minor, he/she is the oldest eligible sibling and no adults are eligible donors.
- Written informed consent from donor. Donors who are minors will be evaluated by a social worker, psychologist or psychiatrist prior to the assent process to determine willingness to participate. If willingness to participate has been confirmed, informed consent will be obtained from adult parent or legal guardian. Informed assent will be obtained from minor donor in the presence of a third party who will assess comprehension and voluntary participation.
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: Treatment of Leukocyte Adhesion Deficiency With Allogeneic Stem Cell Transplantation
This study will investigate the safety and effectiveness of a modified stem cell transplant procedure for treating leukocyte adhesion deficiency (LAD). LAD is an inherited blood disorder of leukocytes (infection-fighting white blood cells) that leaves patients vulnerable to life-threatening infections. Transplantation of donated stem cells (cells produced by the bone marrow that mature into blood cells) can improve the immune system of patients with LAD. 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, T-cells (a type of white blood cell) from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells recognize the patient's cells as foreign and mount an immune response to destroy them. To try to reduce these risks, the donor's T-cells will be removed from the rest of the stem cells to be transplanted.
Patients with LAD who weigh at least 12 kg (26.4 LB), who do not have an active infection, and who have a family member that is a well-matched donor may be eligible for this study. Pregnant or breast feeding women may not participate. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, X-rays or computed tomography (CT) scans of the body, and dental and eye examinations. They will fill out questionnaires that measure emotional well being, quality of life and intelligence (the ability to learn and understand).
Read more
Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to move stem cells from the bone marrow to the bloodstream. The stem cells will be collected by apheresis, where blood is drawn through a needle placed in one arm and pumped into a machine separating and removing the required cells. The rest of the blood is then returned through a needle in the other arm.
Before the transplant, a central venous line (large plastic tube) is placed into a major vein. This tube can stay in the body and be used during the entire treatment period to deliver the donated stem cells, give medications, transfuse blood, if needed, and withdraw blood samples. Several days before the transplant procedure, patients will begin a conditioning regimen of low-dose chemotherapy with cyclophosphamide, fludarabine, and Campath 1H. When the conditioning therapy is completed, the stem cells will be infused. To help prevent rejection of donor cells, cyclosporine will be given by mouth or by vein starting 1 month after the transplant procedure.
The average hospital stay for stem cell transplantation is 21 days. After discharge, patients will return for follow-up clinic visits weekly or twice weekly for 2 to 3 months. These visits will include a symptom check, physical examination, and blood tests. Subsequent visits will be scheduled at 4, 6, 9, and 12 months after the transplant, or more often if required, and then yearly
Read the detailed description
Leukocyte Adhesion Deficiency (LAD) is an inherited disorder of leukocyte function. Patients are profoundly immunocompromised and plagued early in life with recurrent and often life threatening infections. Allogeneic stem cell transplantation significantly improves immune function in patients LAD however severe toxicities are associated with conventional approaches to treatment. The primary objective of this phase II study is to investigate efficacy of a novel approach to allogeneic stem cell transplantation that is designed to promote partial or complete donor stem cell engraftment (hematopoietic chimerism) with reduced transplant morbidity and mortality. In an attempt to reduce toxicity from pre-transplant bone marrow conditioning, a highly immunosuppressive, low intensity bone marrow conditioning regimen will be used. Patients will be transplanted with peripheral blood stem cells from an HLA identical family member. T-lymphocytes will be removed from the stem cell graft in an attempt to decrease the risk of graft vs host disease. Donor T-cells will be infused at various time points following the transplant to augment donor hematopoietic chimerism and aid in immune reconstitution. The primary end points of this study are the establishment of donor hematopoietic chimerism, acute and chronic graft versus host disease, and transplant related mortality.
- Conditions
- Leukocyte-Adhesion Deficiency Syndrome
- Being tested
- modified stem cell transplant
- Keywords
- Non-Myeloablative, Campath 1-H, Fludarabine, Immunodeficiency, Infection, Leukocyte Adhesion Deficiency, LAD
- Medical subject headings
- Leukocyte-Adhesion Deficiency Syndrome, Immunologic Deficiency Syndromes, Infections, Leukocyte adhesion deficiency type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
modified stem cell transplantProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2002 (estimated)
- Study startFeb 2002
- Study completionFeb 2003
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 Leukocyte-Adhesion Deficiency SyndromeStudies 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
- NCT00031005
- Sponsor's protocol ID
- 020126
- Other IDs
- 02-I-0126
- Status last verified
- Feb 2003
- First submitted
- 20 Feb 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Fischer A, Lisowska-Grospierre B, Anderson DC, Springer TA. Leukocyte adhesion deficiency: molecular basis and functional consequences. Immunodefic Rev. 1988;1(1):39-54.
PubMed 3078709von Andrian UH, Berger EM, Ramezani L, Chambers JD, Ochs HD, Harlan JM, Paulson JC, Etzioni A, Arfors KE. In vivo behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. J Clin Invest. 1993 Jun;91(6):2893-7. doi: 10.1172/JCI116535.
PubMed 7685776Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC, Gershoni-Baruch R. Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992 Dec 17;327(25):1789-92. doi: 10.1056/NEJM199212173272505. No abstract available.
PubMed 1279426
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
- Treatment of Leukocyte Adhesion Deficiency With Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00031005
- Acronym / sponsor ID
- 020126
- Conditions
- Leukocyte-Adhesion Deficiency Syndrome
- Keywords
- Non-Myeloablative, Campath 1-H, Fludarabine, Immunodeficiency, Infection, Leukocyte Adhesion Deficiency, LAD
- 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
- Feb 2002
- Study completion
- Feb 2003
- First posted
- 21 Feb 2002 (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 modified stem cell transplant procedure for treating leukocyte adhesion deficiency (LAD). LAD is an inherited blood disorder of leukocytes (infection-fighting white blood cells) that leaves patients vulnerable to life-threatening infections. Transplantation of donated stem cells (cells produced by the bone marrow that mature into blood cells) can improve the immune system of patients with LAD. 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, T-cells (a type of white blood cell) from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells recognize the patient's cells as foreign and mount an immune response to destroy them. To try to reduce these risks, the donor's T-cells will be removed from the rest of the stem cells to be transplanted.
Patients with LAD who weigh at least 12 kg (26.4 LB), who do not have an active infection, and who have a family member that is a well-matched donor may be eligible for this study. Pregnant or breast feeding women may not participate. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, X-rays or computed tomography (CT) scans of the body, and dental and eye examinations. They will fill out questionnaires that measure emotional well being, quality of life and intelligence (the ability to learn and understand).
Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to move stem cells from the bone marrow to the bloodstream. The stem cells will be collected by apheresis, where blood is drawn through a needle placed in one arm and pumped into a machine separating and removing the required cells. The rest of the blood is then returned through a needle in the other arm.
Before the transplant, a central venous line (large plastic tube) is placed into a major vein. This tube can stay in the body and be used during the entire treatment period to deliver the donated stem cells, give medications, transfuse blood, if needed, and withdraw blood samples. Several days before the transplant procedure, patients will begin a conditioning regimen of low-dose chemotherapy with cyclophosphamide, fludarabine, and Campath 1H. When the conditioning therapy is completed, the stem cells will be infused. To help prevent rejection of donor cells, cyclosporine will be given by mouth or by vein starting 1 month after the transplant procedure.
The average hospital stay for stem cell transplantation is 21 days. After discharge, patients will return for follow-up clinic visits weekly or twice weekly for 2 to 3 months. These visits will include a symptom check, physical examination, and blood tests. Subsequent visits will be scheduled at 4, 6, 9, and 12 months after the transplant, or more often if required, and then yearly
Detailed description
Leukocyte Adhesion Deficiency (LAD) is an inherited disorder of leukocyte function. Patients are profoundly immunocompromised and plagued early in life with recurrent and often life threatening infections. Allogeneic stem cell transplantation significantly improves immune function in patients LAD however severe toxicities are associated with conventional approaches to treatment. The primary objective of this phase II study is to investigate efficacy of a novel approach to allogeneic stem cell transplantation that is designed to promote partial or complete donor stem cell engraftment (hematopoietic chimerism) with reduced transplant morbidity and mortality. In an attempt to reduce toxicity from pre-transplant bone marrow conditioning, a highly immunosuppressive, low intensity bone marrow conditioning regimen will be used. Patients will be transplanted with peripheral blood stem cells from an HLA identical family member. T-lymphocytes will be removed from the stem cell graft in an attempt to decrease the risk of graft vs host disease. Donor T-cells will be infused at various time points following the transplant to augment donor hematopoietic chimerism and aid in immune reconstitution. The primary end points of this study are the establishment of donor hematopoietic chimerism, acute and chronic graft versus host disease, and transplant related mortality.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Minimum weight of 12 kg.
- Disease criteria: LAD: less than 20% expression of CD18 (as measured by fluorescence intensity compared to controls) on peripheral leukocytes by flow cytometry and either: a) clinical history of 2 severe infections requiring intravenous anti-bacterial or anti-fungal treatment OR b) history of life-threatening non-healing skin lesions.
- Free of active infection. Patients with non-healing skin lesions may be enrolled after superinfection has been contained.
- Patients with consenting HLA-matched related donors that meet donor selection criteria.
- Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be greater than 40%;
Key exclusion criteria (11 listed)
- Female patients who are pregnant or breast-feeding.
- ECOG performance status of 2 or less or greater than 50% on the Lansky scale for ages 0-10 .
- Seropositivity for HIV.
- Evidence of rapid deterioration due to progressive infection and/or organ damage.
- Malignant diseases liable to relapse or progress within 5 years.
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 |
|---|---|---|
| modified stem cell transplant | 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 3078709Fischer A, Lisowska-Grospierre B, Anderson DC, Springer TA. Leukocyte adhesion deficiency: molecular basis and functional consequences. Immunodefic Rev. 1988;1(1):39-54.
- Background: PubMed 7685776von Andrian UH, Berger EM, Ramezani L, Chambers JD, Ochs HD, Harlan JM, Paulson JC, Etzioni A, Arfors KE. In vivo behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. J Clin Invest. 1993 Jun;91(6):2893-7. doi: 10.1172/JCI116535.
- Background: PubMed 1279426Etzioni A, Frydman M, Pollack S, Avidor I, Phillips ML, Paulson JC, Gershoni-Baruch R. Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency. N Engl J Med. 1992 Dec 17;327(25):1789-92. doi: 10.1056/NEJM199212173272505. No abstract available.
Related trials for Leukocyte-Adhesion Deficiency Syndrome
RecruitingObservational study
Evaluation of Patients With Immune Function Abnormalities
Chronic Granulomatous Disease (CGD), X-Linked Severe Combined Immune Deficiency (XSCID)
RecruitingObservational study
Data Collection Study of Patients With Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT With RIC
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
RecruitingPhase 2
Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
Primary Immunodeficiency (PID), Congenital Bone Marrow Failure Syndromes
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 modified stem cell transplant in people with Leukocyte-Adhesion Deficiency Syndrome, 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 11 inclusion and 11 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 NCT00031005, 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.