Waning Donor ChimerismPhase 2NCT01856582
CD34+ Stem Cell Infusion to Augment Graft Function
A Phase 2 study testing CD34+ in people with Waning Donor Chimerism and Waning Immune Function, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
The purpose of this study is to determine if infusing additional special donor cells will help to improve graft or immune function in previously transplanted children with immune deficiencies and bone marrow failures. Read more about this study
- Who is it for?
- Ages Up to 35 years
- Conditions the study is for
- Waning Donor Chimerism, Waning Immune Function, Primary Immunodeficiency Disease(s)
- What is being tested?
- CD34+
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to 15 Aug 2018
- 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 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- To be eligible for this protocol, patients must have the following:
- Primary immunodeficiency (e.g. SCID, Wiskott-Aldrich and/or other more rare conditions and other bone marrow failure syndromes) with prior allogeneic stem cell transplant.
- Waning donor chimerism or immune function that is inadequate to correct their disease or clinical condition, for which primary transplant was given, as determined by their attending physician.
- Available primary donor.
- Must not have other organ dysfunction deemed by the attending physician to preclude this procedure.
- Age < 35 years at time of transplant
Show all 12Show fewer
- One of the following must be true:
- Patients must have evidence of persistent or recurrent immunodeficiency or thrombocytopenia.
- -OR-
- Primary immunodeficiency disease with known potential to progress to malignant condition if untreated.
- -OR-
- Debilitating secondary disease known to be a consequence of inadequate immune response to known agent or pathogen, uncontrollable by other available medical therapies (e.g. third patient described on page 5).
Who cannot join
- Absence of an available original donor
- Failure to sign consent form, or inability to undergo informed consent process
- Pregnant or lactating female
- Uncontrolled GVHD
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Post Transplant CD34+ Selected Stem Cell Infusion to Augment Graft Function in Children With Primary Immunodeficiency Diseases and Bone Marrow Failure Syndromes
The purpose of this study is to determine if infusing additional special donor cells will help to improve graft or immune function in previously transplanted children with immune deficiencies and bone marrow failures.
Read the detailed description
The purpose of this study is to investigate the usefulness of infusing purified CD34+ cells of donor origin in order to augment graft function in response to declining chimerism after initially performing an allogeneic hematopoietic stem cell transplant (HSCT) for children with primary immunodeficiency diseases. This protocol will be utilized for patients with waning mixed donor chimerism that is inadequate for correction of clinical condition or disease for which stem cell transplant was performed, or for augmentation of immune function. An infusion of selected CD34+ stem cells will be given without any preparative regimen. As the children eligible for this protocol have reduced immune function and pre-existing donor chimerism, we hypothesize that stem cells will be able to engraft and the infusion will augment graft function. This therapy serves as an alternative to a second stem cell transplant that is known to be associated with significant morbidity and mortality. CD34+ stem cells will be collected from the donor used for initial stem cell transplant. Cells will be T-cell depleted (TCD) by performing a CD34 selection using the CliniMACS device (Miltenyi Biotec) in order to prevent development of new or exacerbation of existing graft versus host disease (GVHD), as avoidance of GVHD in nonmalignant diseases is desirable. There is sufficient data showing that mixed donor chimerism is adequate for reverting disease phenotype in certain primary immunodeficiencies. Observations from Europe and CCHMC show that donor chimerism might be boosted by CD34+ stem cell infusion alone without any specific preparative regimen. This therapy is likely to be associated with low toxicity due to the absence of a preparative regimen and lack of exposure to fresh donor cells capable of initiating GVHD, and offers potential significant benefit.
- Conditions
- Waning Donor Chimerism, Waning Immune Function, Primary Immunodeficiency Disease(s), Bone Marrow Failure
- Being tested
- CD34+
- Keywords
- Primary Immunodeficiency Disease(s), Mixed Donor Chimerism, bone marrow failure syndromes, allogeneic hematopoietic stem cell transplant (HSCT), children
- Medical subject headings
- Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34+Biological
CD34+ cells are selected using the CliniMACS System; without preparative regimen
| Study group | Role | What they receive |
|---|---|---|
| CD34+ selected stem cell infusion | Experimental | An infusion of selected CD34+ stem cells will be given without any preparative regimen. Receives: Biological: CD34+ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Showed Successful Augmentation of Graft Function
Successful augmentation of graft function achieved if donor chimerism is doubled compared to the value immediately pre-infusion at 12 months.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2013 (estimated)
- Study startOct 2010
- Primary completion15 Aug 2018
- Study completion15 Aug 2018
Why it stopped: CliniMACS CD34 Reagent System was FDA approved for clinical use; therefore, patients were treated clinically.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Waning Donor ChimerismStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Hoxworth Blood Center
- Responsible party
- Sponsor
- Investigators
- Rebecca Marsh, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01856582
- Sponsor's protocol ID
- 2010-2344
- Status last verified
- Dec 2018
- First submitted
- 15 May 2013
- Last updated
- 22 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Chandra S, Bleesing JJ, Jordan MB, Grimley MS, Khandelwal P, Davies SM, Edwards S, Leemhuis T, Marsh RA. Post-Transplant CD34+ Selected Stem Cell "Boost" for Mixed Chimerism after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation in Children and Young Adults with Primary Immune Deficiencies. Biol Blood Marrow Transplant. 2018 Jul;24(7):1527-1529. doi: 10.1016/j.bbmt.2018.03.013. Epub 2018 Mar 16.
PubMed 29555312
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post Transplant CD34+ Selected Stem Cell Infusion to Augment Graft Function in Children With Primary Immunodeficiency Diseases and Bone Marrow Failure Syndromes
- ClinicalTrials.gov ID
- NCT01856582
- Acronym / sponsor ID
- 2010-2344
- Conditions
- Waning Donor Chimerism, Waning Immune Function, Primary Immunodeficiency Disease(s), Bone Marrow Failure
- Keywords
- Primary Immunodeficiency Disease(s), Mixed Donor Chimerism, bone marrow failure syndromes, allogeneic hematopoietic stem cell transplant (HSCT), children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: CliniMACS CD34 Reagent System was FDA approved for clinical use; therefore, patients were treated clinically.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Hoxworth Blood Center
- Study start
- Oct 2010
- Primary completion
- 15 Aug 2018 (actual)
- Study completion
- 15 Aug 2018 (actual)
- First posted
- 17 May 2013 (estimated)
- Results
- Posted 22 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if infusing additional special donor cells will help to improve graft or immune function in previously transplanted children with immune deficiencies and bone marrow failures.
Detailed description
The purpose of this study is to investigate the usefulness of infusing purified CD34+ cells of donor origin in order to augment graft function in response to declining chimerism after initially performing an allogeneic hematopoietic stem cell transplant (HSCT) for children with primary immunodeficiency diseases. This protocol will be utilized for patients with waning mixed donor chimerism that is inadequate for correction of clinical condition or disease for which stem cell transplant was performed, or for augmentation of immune function. An infusion of selected CD34+ stem cells will be given without any preparative regimen. As the children eligible for this protocol have reduced immune function and pre-existing donor chimerism, we hypothesize that stem cells will be able to engraft and the infusion will augment graft function. This therapy serves as an alternative to a second stem cell transplant that is known to be associated with significant morbidity and mortality. CD34+ stem cells will be collected from the donor used for initial stem cell transplant. Cells will be T-cell depleted (TCD) by performing a CD34 selection using the CliniMACS device (Miltenyi Biotec) in order to prevent development of new or exacerbation of existing graft versus host disease (GVHD), as avoidance of GVHD in nonmalignant diseases is desirable. There is sufficient data showing that mixed donor chimerism is adequate for reverting disease phenotype in certain primary immunodeficiencies. Observations from Europe and CCHMC show that donor chimerism might be boosted by CD34+ stem cell infusion alone without any specific preparative regimen. This therapy is likely to be associated with low toxicity due to the absence of a preparative regimen and lack of exposure to fresh donor cells capable of initiating GVHD, and offers potential significant benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD34+ selected stem cell infusion | Experimental | Biological: CD34+An infusion of selected CD34+ stem cells will be given without any preparative regimen. |
Who may qualify
- Ages
- Up to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Primary immunodeficiency (e.g. SCID, Wiskott-Aldrich and/or other more rare conditions and other bone marrow failure syndromes) with prior allogeneic stem cell transplant.
- Waning donor chimerism or immune function that is inadequate to correct their disease or clinical condition, for which primary transplant was given, as determined by their attending physician.
- Available primary donor.
- Must not have other organ dysfunction deemed by the attending physician to preclude this procedure.
- Age < 35 years at time of transplant
Key exclusion criteria (4 listed)
- Absence of an available original donor
- Failure to sign consent form, or inability to undergo informed consent process
- Pregnant or lactating female
- Uncontrolled GVHD
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 |
|---|---|---|
| CD34+CD34+ cells are selected using the CliniMACS System; without preparative regimen | Biological | CD34+ selected stem cell infusion |
Primary outcome
Number of Participants Who Showed Successful Augmentation of Graft Function
Time frame: 12 months
Successful augmentation of graft function achieved if donor chimerism is doubled compared to the value immediately pre-infusion at 12 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29555312Chandra S, Bleesing JJ, Jordan MB, Grimley MS, Khandelwal P, Davies SM, Edwards S, Leemhuis T, Marsh RA. Post-Transplant CD34+ Selected Stem Cell "Boost" for Mixed Chimerism after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation in Children and Young Adults with Primary Immune Deficiencies. Biol Blood Marrow Transplant. 2018 Jul;24(7):1527-1529. doi: 10.1016/j.bbmt.2018.03.013. Epub 2018 Mar 16.
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.
Rebecca Marsh, MD principal investigator
Children's Hospital Medical Center, Cincinnati
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 CD34+ in people with Waning Donor Chimerism and Waning Immune Function, run by Children's Hospital Medical Center, Cincinnati 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 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: stopped early, as of the sponsor's last update on 22 Nov 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 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 22 Oct 2019). 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 Who Showed Successful Augmentation of Graft Function (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01856582, which also lists 1 linked publication.
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 22 Nov 2019.