Adenosine Deaminase DeficiencyPhase 1NCT00008450
Total-Body Irradiation Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Severe Combined Immunodeficiency Undergoing Donor Bone Marrow Transplant
A Phase 1 study testing Allogeneic Bone Marrow Transplantation, Cyclosporine and Laboratory Biomarker Analysis in people with Adenosine Deaminase Deficiency and Autosomal Recessive Disorder, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This pilot clinical trial studies total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients with severe combined immunodeficiency (SCID) undergoing donor bone marrow transplant. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Adenosine Deaminase Deficiency, Autosomal Recessive Disorder, Immune System Disorder
- What is being tested?
- Allogeneic Bone Marrow Transplantation, Cyclosporine and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 1997to 26 Dec 2018
- Phase
- Phase 1
- 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
- Patients with severe combined immunodeficiency syndrome:
- SCID with presence of B lymphocytes
- X-linked SCID (presence of B lymphocytes)
- Autosomal recessive SCID
- Patients with severe combined immunodeficiency syndrome:
- SCID with absence of T and B lymphocytes
Show all 12Show fewer
- Patients with severe combined immunodeficiency syndrome:
- Purine metabolite deficiencies, deficiencies of the purine metabolites
- Adenosine deaminase (ADA) deficiency
- Purine nucleoside phosphorylase (PNP) deficiency
- DONOR: Related donor who is human leukocyte antigen (HLA) genotypically identical at least at one haplotype and may be genotypically or phenotypically identical for serological typing for HLA-A, B, C, and at the allele level for DRB1 and DQB1; related donors other than siblings must be matched at HLA-A, B, and C (at highest resolution available at the time of donor selection) and at DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing; if more than one HLA-identical sibling is available, priority will be given to the oldest normal donor
- DONOR: Unrelated donors who are prospectively matched for HLA-A, B, C, DRB1 and DQB1 by DNA typing at the highest resolution routinely available at the time of donor selection; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
Who cannot join
- Patients with viral associated T cell immunodeficiency disorders, such as human immunodeficiency virus (HIV)
- Patients with other disease or organ dysfunction that would limit survival to less than 30 days
- DONOR: Identical twin
- DONOR: Pregnancy
- DONOR: HIV seropositive
- DONOR: A positive anti-donor cytotoxic cross match is absolute donor exclusion
- DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-HLA allele mismatch, i.e., the patient is A*0201, and this type of mismatch is not allowed
- DONOR: < 6 months old, > 75 years old
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Induction of Mixed Hematopoietic Chimerism in Patients With Severe Combined Immunodeficiency Disorders Using Allogeneic Bone Marrow and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil
This pilot clinical trial studies total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients with severe combined immunodeficiency (SCID) undergoing donor bone marrow transplant. Giving total-body irradiation (TBI) before a donor bone marrow transplant using stem cells that closely match the patient's stem cells, helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may mix with the patient's immune cells and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
Read the detailed description
PRIMARY OBJECTIVES:
- To safely establish partial lymphoid chimerism (1-95% donor cluster of differentiation [CD]3+ cells) using a non-lethal conditioning regimen in patients with severe combined immunodeficiency syndrome.
II. To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in patients with immunodeficiency diseases.
OUTLINE:
Patients receive cyclosporine orally (PO) or intravenously (IV) on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
After completion of study treatment, patients are followed up at 6 months and then yearly for 5 years.
- Conditions
- Adenosine Deaminase Deficiency, Autosomal Recessive Disorder, Immune System Disorder, Purine-Nucleoside Phosphorylase Deficiency, Severe Combined Immunodeficiency, Severe Combined Immunodeficiency With Absence of T and B Cells
- Being tested
- Allogeneic Bone Marrow Transplantation, Cyclosporine, Laboratory Biomarker Analysis, Mycophenolate Mofetil, Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Severe combined immunodeficiency due to adenosine deaminase deficiency, Immune System Diseases, Purine Nucleoside Phosphorylase Deficiency, Severe Combined Immunodeficiency, X-Linked Combined Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Bone Marrow TransplantationProcedure or surgery
Also called Allo BMT, Allogeneic BMT
Undergo allogeneic bone marrow transplant
CyclosporineDrug
Also called 27-400, Ciclosporin, CsA, Cyclosporin
Given PO or IV
Laboratory Biomarker AnalysisOther
Correlative studies
Also called Cellcept, MMF
Given PO or IV
Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST
Undergo nonmyeloablative allogeneic hematopoietic stem cell transplant
Total-Body IrradiationRadiation
Also called Total Body Irradiation, Whole-Body Irradiation
Undergo TBI
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cyclosporine, mycophenolate mofetil, transplant) | Experimental | Patients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0. Receives: Procedure: Allogeneic Bone Marrow Transplantation; Drug: Cyclosporine; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Radiation: Total-Body Irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases
It will be established whether a non-lethal conditioning regimen can successfully induce mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases, without adverse effects on mortality.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2001 (estimated)
- Study start11 Aug 1997
- Primary completion25 Oct 2011
- Study completion26 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenosine Deaminase DeficiencyStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lauri Burroughs, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00008450
- Sponsor's protocol ID
- 1227.00
- Other IDs
- NCI-2010-02045, 1227.00, P01HL036444, P30CA015704
- Status last verified
- Jul 2019
- First submitted
- 6 Jan 2001
- Last updated
- 29 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction of Mixed Hematopoietic Chimerism in Patients With Severe Combined Immunodeficiency Disorders Using Allogeneic Bone Marrow and Post-Transplant Immunosuppression With Cyclosporine and Mycophenolate Mofetil
- ClinicalTrials.gov ID
- NCT00008450
- Acronym / sponsor ID
- 1227.00
- Conditions
- Adenosine Deaminase Deficiency, Autosomal Recessive Disorder, Immune System Disorder, Purine-Nucleoside Phosphorylase Deficiency, Severe Combined Immunodeficiency, Severe Combined Immunodeficiency With Absence of T and B Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 11 Aug 1997 (actual)
- Primary completion
- 25 Oct 2011 (actual)
- Study completion
- 26 Dec 2018 (actual)
- First posted
- 8 Jan 2001 (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 pilot clinical trial studies total-body irradiation followed by cyclosporine and mycophenolate mofetil in treating patients with severe combined immunodeficiency (SCID) undergoing donor bone marrow transplant. Giving total-body irradiation (TBI) before a donor bone marrow transplant using stem cells that closely match the patient's stem cells, helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may mix with the patient's immune cells and help destroy any remaining abnormal cells. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
Detailed description
PRIMARY OBJECTIVES:
- To safely establish partial lymphoid chimerism (1-95% donor cluster of differentiation [CD]3+ cells) using a non-lethal conditioning regimen in patients with severe combined immunodeficiency syndrome.
II. To define the kinetics of immune reconstitution following a non-lethal conditioning regimen in patients with immunodeficiency diseases.
OUTLINE:
Patients receive cyclosporine orally (PO) or intravenously (IV) on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0.
After completion of study treatment, patients are followed up at 6 months and then yearly for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cyclosporine, mycophenolate mofetil, transplant) | Experimental | Procedure: Allogeneic Bone Marrow Transplantation, Drug: Cyclosporine, Other: Laboratory Biomarker Analysis, Drug: Mycophenolate Mofetil, Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation, Radiation: Total-Body IrradiationPatients receive cyclosporine PO or IV on days -3 to 100 followed by a taper until day 180 and mycophenolate mofetil PO or IV on days 0-40 with a taper until day 96 in the absence of unacceptable toxicity. Unrelated donor recipients also undergo TBI on day 0. Patients undergo bone marrow transplant on day 0. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Patients with severe combined immunodeficiency syndrome:
- Patients with severe combined immunodeficiency syndrome:
- Patients with severe combined immunodeficiency syndrome:
- DONOR: Related donor who is human leukocyte antigen (HLA) genotypically identical at least at one haplotype and may be genotypically or phenotypically identical for serological typing for HLA-A, B, C, and at the allele level for DRB1 and DQB1; related donors other than siblings must be matched at HLA-A, B, and C (at highest resolution available at the time of donor selection) and at DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing; if more than one HLA-identical sibling is available, priority will be given to the oldest normal donor
- DONOR: Unrelated donors who are prospectively matched for HLA-A, B, C, DRB1 and DQB1 by DNA typing at the highest resolution routinely available at the time of donor selection; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
Key exclusion criteria (8 listed)
- Patients with viral associated T cell immunodeficiency disorders, such as human immunodeficiency virus (HIV)
- Patients with other disease or organ dysfunction that would limit survival to less than 30 days
- DONOR: Identical twin
- DONOR: Pregnancy
- DONOR: HIV seropositive
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 |
|---|---|---|
| Allogeneic Bone Marrow TransplantationAlso: Allo BMT, Allogeneic BMTUndergo allogeneic bone marrow transplant | Procedure or surgery | Treatment (cyclosporine, mycophenolate mofetil, transplant) |
| CyclosporineAlso: 27-400, Ciclosporin, CsA, CyclosporinGiven PO or IV | Drug | Treatment (cyclosporine, mycophenolate mofetil, transplant) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (cyclosporine, mycophenolate mofetil, transplant) |
| Mycophenolate MofetilAlso: Cellcept, MMFGiven PO or IV | Drug | Treatment (cyclosporine, mycophenolate mofetil, transplant) |
| Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationAlso: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NSTUndergo nonmyeloablative allogeneic hematopoietic stem cell transplant | Procedure or surgery | Treatment (cyclosporine, mycophenolate mofetil, transplant) |
| Total-Body IrradiationAlso: Total Body Irradiation, Whole-Body IrradiationUndergo TBI | Radiation | Treatment (cyclosporine, mycophenolate mofetil, transplant) |
Primary outcome
Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases
Time frame: Up to 5 years
It will be established whether a non-lethal conditioning regimen can successfully induce mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases, without adverse effects on mortality.
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 29 Jul 2019.
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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.
Lauri Burroughs principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Allogeneic Bone Marrow Transplantation, Cyclosporine and Laboratory Biomarker Analysis in people with Adenosine Deaminase Deficiency and Autosomal Recessive Disorder, run by Fred Hutchinson Cancer Center 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 12 inclusion and 8 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 29 Jul 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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.
What does the primary outcome measure?
Mixed hematopoietic chimerism in a population of pediatric patients with immunodeficiency diseases (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jul 2019.