Bone Marrow Failure SyndromePhase 1/2NCT01966367
CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
A Phase 1/2 study testing CD34 Stem Cell Selection Therapy in people with Bone Marrow Failure Syndrome and Severe Aplastic Anemia, run by Diane George at 1 site in United States.
Trial summary
This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune… Read more about this study
- Who is it for?
- Ages Up to 40 years
- Conditions the study is for
- Bone Marrow Failure Syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia
- What is being tested?
- CD34 Stem Cell Selection Therapy
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Feb 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- General Eligibility (All Patients)
- Patient must be < or = 40 years of age. Patients with sickle cell anemia must be at least 2 years of age.
- Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
- Approval for the use of this treatment protocol by the individual institution's Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U. S. Department of Health and Human Services.
- Human leukocyte antigen (HLA) typing will be performed by high-resolution molecular DNA typing for HLA Class I A, B, and C and HLA Class II DRB1 and DQB1 alleles.
- Unrelated donor: An 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry.
Show all 20Show fewer
- Related Donor: A 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 matched (or partially matched) family donor will be required for study entry.
- Non-malignant Disorders per protocol.
- Hemoglobinopathies per protocol.
- Requirement for CD34+ stem cell selection for a second infusion of stem cells following an allogeneic stem cell transplant from a related or unrelated adult donor.
- Additional eligibility for patients with non-malignant disorders receiving myeloablative conditioning
- Adequate renal function as determined by the institutional normal range.
- Adequate liver function per protocol.
- Adequate cardiac function defined by radionucleotide angiogram or echocardiogram.
- Adequate pulmonary function by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air.
- Additional eligibility for patients with non-malignant disorders receiving reduced intensity conditioning
- Adequate renal function as determined by the institutional normal range.
- Adequate liver function per protocol.
- Adequate cardiac function per protocol.
- Adequate pulmonary function per protocol.
Who cannot join
- Patients with documented uncontrolled infection at the time of study entry are not eligible.
- Pregnancy/Breast-Feeding Females who are pregnant or breast feeding at the time of study entry are not eligible.
- -- The following additional exclusion criteria for patients with sickle cell anemia the following exclusion criteria also apply
- Patients with bridging fibrosis or cirrhosis of the liver.
- Uncontrolled bacterial, viral or fungal infection in the past month.
- Seropositivity for HIV.
- Patients who have received prior hematocrit (HCT) within three months of enrollment for reduced intensity regimen and within six months for myeloablative regimen/reduced toxicity regimens.
Trial locations and contacts
1 site in 1 country.
United States1 site
Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University
New York, New York, 10032
About this study
Official title: CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplantation for Non-Malignant Disease
This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune reconstitution (including normalization of T, B and natural killer (NK) cell repertoire and Immunoglobulin G production), and to establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a non-malignant disease.
Read the detailed description
Graft-versus-host disease (GVHD) is a condition that results from a reaction of transplanted donor T-lymphocytes against the body and organs of the patient receiving the transplanted cells. There are two forms: acute (early) and chronic (late). Acute GVHD may produce skin rashes, liver disease, diarrhea, and an increased risk of infection. Chronic GVHD can appear in patients without prior acute GVHD. Chronic GVHD may also produce skin rashes, liver disease, diarrhea and an increased risk of infection. GVHD can make patients very sick, and have GVHD can make it more likely that patients will not survive their transplant. In this study, the investigators are offering to treat the donor peripheral blood stem cells in the hope that it will make it less likely for the patient who receives them from having GVHD.
Patients on this study are being offered an experimental treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec, Germany), a CD34+ selection device to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+ stem cells are selected from the donor's peripheral blood stem cells. In doing this, T-cells are also removed. T-cells are the cells which are responsible for graft versus host disease (GVHD). This study is a clinical trial for patients diagnosed with a non-malignant disease who will receive a peripheral blood stem cell transplant. Patients with the following types of non-malignant diseases can participate in this study: Bone marrow failure syndromes (including Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia (Kostmann's Syndrome), Diamond-Blackfan Anemia, Schwachman Diamond Syndrome, Primary Immunodeficiency Syndromes, Acquired Immunodeficiency Syndromes, and Histiocytic Disorders) and Hemoglobinopathies (including Sickle Cell Anemia and Sickle/Beta Thalassemia). Patients on this study will be given standard transplant therapy with either high doses of chemotherapy drugs or lower doses of chemotherapy drugs, depending on their disease. Diseases within each disease group will receive chemotherapy that is standard for that condition.
Some patients on this study will receive an allogeneic stem cell transplant (AlloSCT) from a matched related donor. If a patient does not have a matched related donor, a bone marrow search will be done at all of the bone marrow banks in the world. The patient will then go on to receive an AlloSCT from either a partially matched family member or an unrelated adult stem cell transplant donor. The transplanted cells will allow all the normal parts of the patient's blood system to recover. The experimental portion of this treatment involves the use of a Miltenyi CliniMACS CD34+ selection device to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+ stem cell selection AlloSCT has been studied in adults with the malignant and non-malignant disease with successful engraftment and has shown some improvement in GVHD. It is unknown if CD34+ stem cell selection will work to prevent severe GVHD in children and adolescents.
- Conditions
- Bone Marrow Failure Syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia, Diamond-Blackfan Anemia, Schwachman Diamond Syndrome
- Being tested
- CD34 Stem Cell Selection Therapy
- Keywords
- Unrelated donor transplant, Haploidentical donor transplant, Peripheral blood stem cell transplantation, CD34+ selection, Non-malignant disease, Bone marrow failure syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia, Diamond-Blackfan Anemia, Schwachman Diamond Syndrome, Primary Immunodeficiency Syndrome, Acquired Immunodeficiency Syndrome, Histiocytic Syndrome, Familial Hemophagocytic Lymphocytosis, Lymphohistiocytosis, Macrophage Activation Syndrome, Langerhans Cell Histiocytosis (LCH), Hemoglobinopathies, Sickle Cell Disease
- Medical subject headings
- Bone Marrow Failure Disorders, Anemia, Aplastic, Neutropenia, Severe Congenital, Autosomal Recessive 3, Anemia, Diamond-Blackfan, Shwachman-Diamond Syndrome, Primary Immunodeficiency Diseases, Acquired Immunodeficiency Syndrome, Histiocytosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD34 Stem Cell Selection TherapyBiological
The CliniMACS (PLUS) Reagent System (Miltenyi CliniMACS CD34+ Cell Selection Device) will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD).
| Study group | Role | What they receive |
|---|---|---|
| CliniMACS PLUS followed by chemotherapy | Experimental | Patients will receive a pre-transplant conditioning regimen of Busulfan Fludarabine and Alemtuzumab. For patients with pre-transplant hepatic dysfunction, Melphalan will be substituted for the Busulfan. For patients receiving a second transplant or a "boost", pre-transplant conditioning based on the clinical condition of the patient will be determined by the Principal Investigator and the patient's bone marrow transplantation (BMT) physician. The donor peripheral blood stem cells will undergo CD34+ selection (Biological/Vaccine: CD34 Stem Cell Selection Therapy). The CliniMACS (PLUS) Reagent System will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD). Receives: Biological: CD34 Stem Cell Selection Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of acute graft versus host disease (GVHD)
Determine the incidence and severity of acute GVHD.
Measured: 100 days
Secondary outcomes (6)
Incidence of primary graft failure
Quantify the incidence of primary and secondary graft failure.
Measured: 1 year
Survival Rate
To assess event free survival and overall survival
Measured: 5 years
Time to neutrophil and platelet engraftment
To determine the time to neutrophil and platelet engraftment
Measured: 1 year
Time to immune reconstitution
To determine the time to immune reconstitution (including normalization of T, B and NK cell repertoire and Immunoglobulin G production)
Measured: 2 years
Incidence of infectious complications
To establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections
Measured: 2 years
Incidence of secondary graft failure
Quantify the incidence of primary and secondary graft failure.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2013 (estimated)
- Study startMar 2013
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Marrow Failure SyndromeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diane George
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Diane George, Columbia University
- Investigators
- Diane George, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01966367
- Sponsor's protocol ID
- AAAL0156
- Status last verified
- Aug 2025
- First submitted
- 17 Oct 2013
- Last updated
- 14 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplantation for Non-Malignant Disease
- ClinicalTrials.gov ID
- NCT01966367
- Acronym / sponsor ID
- AAAL0156
- Conditions
- Bone Marrow Failure Syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia, Diamond-Blackfan Anemia, Schwachman Diamond Syndrome
- Keywords
- Unrelated donor transplant, Haploidentical donor transplant, Peripheral blood stem cell transplantation, CD34+ selection, Non-malignant disease, Bone marrow failure syndrome, Severe Aplastic Anemia, Severe Congenital Neutropenia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Diane GeorgeUniversity, hospital or other
- Study start
- Mar 2013 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 21 Oct 2013 (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's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft rejection, to assess event free survival and overall survival, to determine the time to neutrophil and platelet engraftment, to determine the time to immune reconstitution (including normalization of T, B and natural killer (NK) cell repertoire and Immunoglobulin G production), and to establish the incidence of infectious complications including bacterial, viral, fungal and atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a non-malignant disease.
Detailed description
Graft-versus-host disease (GVHD) is a condition that results from a reaction of transplanted donor T-lymphocytes against the body and organs of the patient receiving the transplanted cells. There are two forms: acute (early) and chronic (late). Acute GVHD may produce skin rashes, liver disease, diarrhea, and an increased risk of infection. Chronic GVHD can appear in patients without prior acute GVHD. Chronic GVHD may also produce skin rashes, liver disease, diarrhea and an increased risk of infection. GVHD can make patients very sick, and have GVHD can make it more likely that patients will not survive their transplant. In this study, the investigators are offering to treat the donor peripheral blood stem cells in the hope that it will make it less likely for the patient who receives them from having GVHD.
Patients on this study are being offered an experimental treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec, Germany), a CD34+ selection device to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+ stem cells are selected from the donor's peripheral blood stem cells. In doing this, T-cells are also removed. T-cells are the cells which are responsible for graft versus host disease (GVHD). This study is a clinical trial for patients diagnosed with a non-malignant disease who will receive a peripheral blood stem cell transplant. Patients with the following types of non-malignant diseases can participate in this study: Bone marrow failure syndromes (including Severe Aplastic Anemia, Severe Congenital Neutropenia, Amegakaryocytic Thrombocytopenia (Kostmann's Syndrome), Diamond-Blackfan Anemia, Schwachman Diamond Syndrome, Primary Immunodeficiency Syndromes, Acquired Immunodeficiency Syndromes, and Histiocytic Disorders) and Hemoglobinopathies (including Sickle Cell Anemia and Sickle/Beta Thalassemia). Patients on this study will be given standard transplant therapy with either high doses of chemotherapy drugs or lower doses of chemotherapy drugs, depending on their disease. Diseases within each disease group will receive chemotherapy that is standard for that condition.
Some patients on this study will receive an allogeneic stem cell transplant (AlloSCT) from a matched related donor. If a patient does not have a matched related donor, a bone marrow search will be done at all of the bone marrow banks in the world. The patient will then go on to receive an AlloSCT from either a partially matched family member or an unrelated adult stem cell transplant donor. The transplanted cells will allow all the normal parts of the patient's blood system to recover. The experimental portion of this treatment involves the use of a Miltenyi CliniMACS CD34+ selection device to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. CD34+ stem cell selection AlloSCT has been studied in adults with the malignant and non-malignant disease with successful engraftment and has shown some improvement in GVHD. It is unknown if CD34+ stem cell selection will work to prevent severe GVHD in children and adolescents.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CliniMACS PLUS followed by chemotherapy | Experimental | Biological: CD34 Stem Cell Selection TherapyPatients will receive a pre-transplant conditioning regimen of Busulfan Fludarabine and Alemtuzumab. For patients with pre-transplant hepatic dysfunction, Melphalan will be substituted for the Busulfan. For patients receiving a second transplant or a "boost", pre-transplant conditioning based on the clinical condition of the patient will be determined by the Principal Investigator and the patient's bone marrow transplantation (BMT) physician. The donor peripheral blood stem cells will undergo CD34+ selection (Biological/Vaccine: CD34 Stem Cell Selection Therapy). The CliniMACS (PLUS) Reagent System will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD). |
Who may qualify
- Ages
- Up to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- General Eligibility (All Patients)
- Additional eligibility for patients with non-malignant disorders receiving myeloablative conditioning
- Additional eligibility for patients with non-malignant disorders receiving reduced intensity conditioning
Key exclusion criteria (7 listed)
- Patients with documented uncontrolled infection at the time of study entry are not eligible.
- Pregnancy/Breast-Feeding Females who are pregnant or breast feeding at the time of study entry are not eligible.
- -- The following additional exclusion criteria for patients with sickle cell anemia the following exclusion criteria also apply
- Patients with bridging fibrosis or cirrhosis of the liver.
- Uncontrolled bacterial, viral or fungal infection in the past month.
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 Stem Cell Selection TherapyThe CliniMACS (PLUS) Reagent System (Miltenyi CliniMACS CD34+ Cell Selection Device) will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD). | Biological | CliniMACS PLUS followed by chemotherapy |
Primary outcome
Incidence of acute graft versus host disease (GVHD)
Time frame: 100 days
Determine the incidence and severity of acute GVHD.
6 secondary outcomes
Incidence of primary graft failure
Time frame: 1 year
Survival Rate
Time frame: 5 years
Time to neutrophil and platelet engraftment
Time frame: 1 year
Time to immune reconstitution
Time frame: 2 years
Incidence of infectious complications
Time frame: 2 years
Incidence of secondary graft failure
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2025.
- Individual participant dataSharing planned: Undecided
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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.
Diane George, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CD34 Stem Cell Selection Therapy in people with Bone Marrow Failure Syndrome and Severe Aplastic Anemia, run by Diane George 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 20 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2025. 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 combined 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.
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?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of acute graft versus host disease (GVHD) (time frame: 100 days). 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 14 Aug 2025.