Bone Marrow Failure SyndromesPhase 2MiniCliniNCT02277639
Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
A Phase 2 study testing CliniMACs device in people with Bone Marrow Failure Syndromes and Immunodeficiencies, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age. Read more about this study
- Who is it for?
- Ages Up to 22 years
- Conditions the study is for
- Bone Marrow Failure Syndromes, Immunodeficiencies, Immune Dysregulation Syndromes
- What is being tested?
- CliniMACs device
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Bone marrow failure syndromes for which SCT is indicated, including severe aplastic anemia refractory to non transplant therapies congenital neutropenia, congenital thrombocytopenia, congenital red cell aplasia
- Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome, IPEX syndrome, X-linked lymphoproliferative disease
- Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other MAS refractory to standard therapy
- Organ function clearance
Who cannot join
- Uncontrolled bacterial, viral or fungal infections
- HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.
- Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes
- Pregnant Females
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.
Read the detailed description
This study will allow transplantation using a reduced intensity conditioning regimen for children with non-malignant diseases who lack a matched related or unrelated donor. Donors will be unrelated or partially matched related, depending upon urgency and availability. If each parent is haploidentical, the mother will be preferred, as there is evidence of reduced transplant related mortality and superior survival with a maternal donor. The risks of severe graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning immune suppression with Thymoglobulin. It is recommended that patients with immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on non-engraftment and hyperinflammatory states.
Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to allow immune reconstitution.
- Being tested
- CliniMACs device
- Keywords
- Transplant related mortality, Graft versus host disease, Bone marrow transplant
- Medical subject headings
- Bone Marrow Failure Disorders, 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.
CliniMACs deviceDevice
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
| Study group | Role | What they receive |
|---|---|---|
| Bone Marrow Failure Syndrome | Experimental | Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. Receives: Device: CliniMACs device |
| Immunodeficiency / Dysregulation | Experimental | Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. Receives: Device: CliniMACs device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Engraftment
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Measured: One Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2014 (estimated)
- Study startNov 2011
- Primary completionMar 2016
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bone Marrow Failure SyndromesStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nancy Bunin, Children's Hospital of Philadelphia
- Investigators
- Nancy Bunin, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02277639
- Sponsor's protocol ID
- 11-008330
- Other IDs
- CHP 980
- Acronym
- MiniClini
- Status last verified
- Mar 2018
- First submitted
- 22 Oct 2014
- Last updated
- 11 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
- ClinicalTrials.gov ID
- NCT02277639
- Acronym / sponsor ID
- MiniClini / 11-008330
- Keywords
- Transplant related mortality, Graft versus host disease, Bone marrow transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 29 Oct 2014 (estimated)
- Results
- Posted 11 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.
Detailed description
This study will allow transplantation using a reduced intensity conditioning regimen for children with non-malignant diseases who lack a matched related or unrelated donor. Donors will be unrelated or partially matched related, depending upon urgency and availability. If each parent is haploidentical, the mother will be preferred, as there is evidence of reduced transplant related mortality and superior survival with a maternal donor. The risks of severe graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning immune suppression with Thymoglobulin. It is recommended that patients with immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on non-engraftment and hyperinflammatory states.
Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to allow immune reconstitution.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
| Arm | Type | Receives |
|---|---|---|
| Bone Marrow Failure Syndrome | Experimental | Device: CliniMACs deviceReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. |
| Immunodeficiency / Dysregulation | Experimental | Device: CliniMACs deviceReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion. |
Who may qualify
- Ages
- Up to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Bone marrow failure syndromes for which SCT is indicated, including severe aplastic anemia refractory to non transplant therapies congenital neutropenia, congenital thrombocytopenia, congenital red cell aplasia
- Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome, IPEX syndrome, X-linked lymphoproliferative disease
- Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other MAS refractory to standard therapy
- Organ function clearance
Key exclusion criteria (4 listed)
- Uncontrolled bacterial, viral or fungal infections
- HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.
- Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes
- Pregnant Females
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 |
|---|---|---|
| CliniMACs deviceReduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. | Device | Bone Marrow Failure Syndrome, Immunodeficiency / Dysregulation |
Primary outcome
Number of Participants With Engraftment
Time frame: One Year
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Nancy Bunin, MD principal investigator
Children's Hospital of Philadelphia
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 CliniMACs device in people with Bone Marrow Failure Syndromes and Immunodeficiencies, run by Children's Hospital of Philadelphia 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 4 inclusion and 4 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 11 Apr 2018. 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?
Yes. Results are posted in the registry (first posted 11 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Engraftment (time frame: One Year). 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 11 Apr 2018.