Myeloid ChimerismPhase 1/2NCT04008368
Repeat Peripheral Blood Stem Cell Transplantation for Patients With Sickle Cell Disease and Falling Donor Myeloid Chimerism Levels
A Phase 1/2 study testing CliniMACS CD34 Reagent in people with Myeloid Chimerism, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Sickle cell disease can often be treated with blood stem cell transplants. But for some people the disease returns. This study will give a second transplant to people whose disease has returned but still have some donor cells in their body. Read more about this study
- Who is it for?
- Ages 2 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Myeloid Chimerism
- What is being tested?
- CliniMACS CD34 Reagent
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2019to 1 Dec 2037
- 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 2 to 80 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patient with history of SCD or beta thalassemia who previously underwent allogeneic hematopoietic stem cell transplantation (HSCT)
- Patient with recurrent SCD defined as HbS greater than or equal to 50% for donors with sickle cell trait and greater than or equal to 10% for donors with HbAA with recurrent clinical manifestations (for example but not limited to recurrent painful crises, acute chest syndrome, priapism, or severe anemia) or patients with recurrent beta thalassemia defined as clinical manifestations such as transfusion-dependence or evidence of extramedullary hematopoiesis. The HbS requirement may be waived by the PI or designee for reasons such as the patient is requiring chronic transfusion therapy or otherwise meets clinical criteria for return of SCD.
- Persistent donor chimerism levels
- Age greater than or equal to 4 years
- Negative beta-HCG
- Ejection fraction greater than or equal to 35%
- DLCO greater than or equal to 35% (Note: This criterion may be omitted in young children (e.g. near the age of 5 years old) or other individuals who may have difficulty understanding or complying with the instructions for accurate testing.)
- Related donor from original transplant, deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Age >= 2 years <80 years old
Who cannot join
- ECOG performance status of 3 or more or if <16 years of age Lansky score of 50 or lower.
- Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to signing the consent
- Patients with fever or suspected minor infection should await resolution of symptoms before signing the consent
- Major anticipated illness or organ failure incompatible with survival from PBSC transplant
- Pregnant or breastfeeding
- History of secondary malignancies (other than localized skin cancer)
- Donor-specific HLA antibodies with mean fluorescent intensity >= 2,000
- None
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: Repeat Peripheral Blood Stem Cell Transplantation for Patients With Sickle Cell Disease or Beta-Thalassemia and Falling Donor Myeloid Chimerism Levels
Background:
Sickle cell disease can often be treated with blood stem cell transplants. But for some people the disease returns. This study will give a second transplant to people whose disease has returned but still have some donor cells in their body.
Read more
Objective:
To cure people s sickle cell disease by giving a second treatment that makes more room in their bone marrow for donor cells.
Eligibility:
People ages 4 and older with sickle cell disease who had a transplant but the disease returned, and their donor relatives. Donors can be 2 years of age or older.
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Recipients will also be screened with heart and breathing tests, x-rays, a bone marrow sample, and teeth and eye exams. They must have a caregiver.
Donors will have 7-8 visits. They will take a drug for 5-6 days to prepare them for the donation. For the donation, blood is taken from a vein in the arm or groin. The stem cells are collected. The rest of the blood is returned. This may be repeated.
Recipients will get a long IV line in their arm or chest for about 1-2 months. They will take drugs to help their body accept the donor cells. They will get the donor cells and red blood cell transfusions through the line. They will stay in the hospital about 30 days after the transfusion of donor cells.
In first 3 months after the infusion, recipients will have many visits. Then they will have visits every 6 months to 1 year for 5 years. During those visits they will repeat some of the screening tests....
Read the detailed description
Nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers. Our ongoing protocol for patients with severe congenital anemias, particularly sickle cell disease (SCD), and an HLA-matched sibling donor has had excellent preliminary results. None of the patients who engrafted had sickle-related events or any evidence of graft versus host disease (GVHD). There was no significant toxicity associated with the conditioning regimen. An additional protocol is ongoing for patients with high risk of graft rejection which employs pentostatin and oral cyclophosphamide (PC) pre-transplant to further deplete recipient lymphocytes in an attempt to decrease the rate of graft rejection, and to date the engraftment rate has substantially improved. Our first haploidentical transplant protocol showed improving engraftment and success rates with the addition of post-transplant cyclophosphamide, but with a median follow-up of 5 years, the disease-free survival was at best 50%. Our new haploidentical transplant protocol has had some encouraging early results in the first 5 patients transplanted.
Based on 67 patients undergoing HLA-matched sibling or haploidentical PBSC transplants at the NIH, we sought to determine what donor chimerism level is necessary to reverse SCD. Three of the patients had falling donor myeloid chimerism (DMC) levels, and when the DMC level fell below 20%, all 3 patients had return of their SCD. Our mathematical model showed that only 20% DMC (which tracks with donor erythroid chimerism) is necessary due to vast differences in donor and recipient red blood cell (RBC) survival. As all 3 patients had persistent but insufficient donor chimerism levels, we performed a PBSC boost using the same donor and busulfan/alemtuzumab conditioning. Haploidentical patients received CD34-selected PBSCs and HLA-matched sibling patients received unmanipulated PBSCs. All 3 patients now remain free of SCD with DMC levels of 100% at 1, 2.5, and 3.5 years post-transplant. Because the same donor was used and no patient experienced graft rejection, the failure of the original protocols likely was due to insufficient myelosuppression and not insufficient immunosuppression. Therefore, in this protocol, we propose repeat PBSC transplants using increased myelosuppression and CD34-selected PBSCs in patients with a haploidentical donor or unmanipulated PBSCs in patients with an HLA-matched sibling donor from the same donor in a population of patients who have falling DMC and return of SCD.
- Conditions
- Myeloid Chimerism
- Being tested
- CliniMACS CD34 Reagent
- Keywords
- Stem Cell Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CliniMACS CD34 ReagentDevice
Haploidentical recipients will receive CD34-selected cells using Miltenyi CliniMACS(R) CD34+ cell selection kits. The target CD34+ cell dose is at least 10 x 106/kg, and the minimum CD34+ cell dose is 5 x 106/kg. All of the cells collected during the apheresis procedure will be given. The cells will be cryopreserved and stored until the day of transplant.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | patients with HLA-matched sibling donors Receives: Device: CliniMACS CD34 Reagent |
| 2 | Other | patients with haploidentical donors Receives: Device: CliniMACS CD34 Reagent |
What is being measured
The primary outcome is the main question the study is designed to answer.
dichotomous positive/negative outcome where a positive response is defined by absence of graft rejection
The primary endpoint for each individual is a dichotomous positive/negative outcome where a positive response is defined by absence of graft rejection, and absence of severe acute GVHD (grade 3 and higher), or moderate to severe chronic GVHD evaluated 100 days post-transplant.
Measured: 5 years
Secondary outcomes (1)
Incidence of graft rejection defined as HbS >10% when donors have HbAA and HbS >50% when donors have sickle cell trait
- Incidence of graft rejection defined as HbS >10% when donors have HbAA and HbS >50% when donors have sickle cell trait 2) Incidence of acute and chronic GVHD 3) The level of chimerism required to maintain both graft survival as well as hematologic normalcy. 4) Incidence of donor type hemoglobin at 1 year post-transplant in SCD patients who have not been transfused in the previous 3 months. 5) Incidence of viral reactivation and disease 6) Disease-free survival and overall survival 7) Relapse rate and graft rejection rate 8) Transplant-related mortality 9) Effects of transplant on organ function 10) Biomarkers associated with tolerance induction
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start24 Oct 2019
- Primary completion30 Jan 2030 (estimated)
- Study completion1 Dec 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myeloid ChimerismStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Courtney F Joseph, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04008368
- Sponsor's protocol ID
- 190118
- Other IDs
- 19-H-0118
- Status last verified
- 22 Oct 2026
- First submitted
- 3 Jul 2019
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repeat Peripheral Blood Stem Cell Transplantation for Patients With Sickle Cell Disease or Beta-Thalassemia and Falling Donor Myeloid Chimerism Levels
- ClinicalTrials.gov ID
- NCT04008368
- Acronym / sponsor ID
- 190118
- Conditions
- Myeloid Chimerism
- Keywords
- Stem Cell Transplant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 30 Jan 2030 (estimated)
- Study completion
- 1 Dec 2037 (estimated)
- First posted
- 5 Jul 2019 (actual)
- 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.
Background:
Sickle cell disease can often be treated with blood stem cell transplants. But for some people the disease returns. This study will give a second transplant to people whose disease has returned but still have some donor cells in their body.
Objective:
To cure people s sickle cell disease by giving a second treatment that makes more room in their bone marrow for donor cells.
Eligibility:
People ages 4 and older with sickle cell disease who had a transplant but the disease returned, and their donor relatives. Donors can be 2 years of age or older.
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Recipients will also be screened with heart and breathing tests, x-rays, a bone marrow sample, and teeth and eye exams. They must have a caregiver.
Donors will have 7-8 visits. They will take a drug for 5-6 days to prepare them for the donation. For the donation, blood is taken from a vein in the arm or groin. The stem cells are collected. The rest of the blood is returned. This may be repeated.
Recipients will get a long IV line in their arm or chest for about 1-2 months. They will take drugs to help their body accept the donor cells. They will get the donor cells and red blood cell transfusions through the line. They will stay in the hospital about 30 days after the transfusion of donor cells.
In first 3 months after the infusion, recipients will have many visits. Then they will have visits every 6 months to 1 year for 5 years. During those visits they will repeat some of the screening tests....
Detailed description
Nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers. Our ongoing protocol for patients with severe congenital anemias, particularly sickle cell disease (SCD), and an HLA-matched sibling donor has had excellent preliminary results. None of the patients who engrafted had sickle-related events or any evidence of graft versus host disease (GVHD). There was no significant toxicity associated with the conditioning regimen. An additional protocol is ongoing for patients with high risk of graft rejection which employs pentostatin and oral cyclophosphamide (PC) pre-transplant to further deplete recipient lymphocytes in an attempt to decrease the rate of graft rejection, and to date the engraftment rate has substantially improved. Our first haploidentical transplant protocol showed improving engraftment and success rates with the addition of post-transplant cyclophosphamide, but with a median follow-up of 5 years, the disease-free survival was at best 50%. Our new haploidentical transplant protocol has had some encouraging early results in the first 5 patients transplanted.
Based on 67 patients undergoing HLA-matched sibling or haploidentical PBSC transplants at the NIH, we sought to determine what donor chimerism level is necessary to reverse SCD. Three of the patients had falling donor myeloid chimerism (DMC) levels, and when the DMC level fell below 20%, all 3 patients had return of their SCD. Our mathematical model showed that only 20% DMC (which tracks with donor erythroid chimerism) is necessary due to vast differences in donor and recipient red blood cell (RBC) survival. As all 3 patients had persistent but insufficient donor chimerism levels, we performed a PBSC boost using the same donor and busulfan/alemtuzumab conditioning. Haploidentical patients received CD34-selected PBSCs and HLA-matched sibling patients received unmanipulated PBSCs. All 3 patients now remain free of SCD with DMC levels of 100% at 1, 2.5, and 3.5 years post-transplant. Because the same donor was used and no patient experienced graft rejection, the failure of the original protocols likely was due to insufficient myelosuppression and not insufficient immunosuppression. Therefore, in this protocol, we propose repeat PBSC transplants using increased myelosuppression and CD34-selected PBSCs in patients with a haploidentical donor or unmanipulated PBSCs in patients with an HLA-matched sibling donor from the same donor in a population of patients who have falling DMC and return of SCD.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Device: CliniMACS CD34 Reagentpatients with HLA-matched sibling donors |
| 2 | Other | Device: CliniMACS CD34 Reagentpatients with haploidentical donors |
Who may qualify
- Ages
- 2 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patient with history of SCD or beta thalassemia who previously underwent allogeneic hematopoietic stem cell transplantation (HSCT)
- Patient with recurrent SCD defined as HbS greater than or equal to 50% for donors with sickle cell trait and greater than or equal to 10% for donors with HbAA with recurrent clinical manifestations (for example but not limited to recurrent painful crises, acute chest syndrome, priapism, or severe anemia) or patients with recurrent beta thalassemia defined as clinical manifestations such as transfusion-dependence or evidence of extramedullary hematopoiesis. The HbS requirement may be waived by the PI or designee for reasons such as the patient is requiring chronic transfusion therapy or otherwise meets clinical criteria for return of SCD.
- Persistent donor chimerism levels
- Age greater than or equal to 4 years
- Negative beta-HCG
Key exclusion criteria (8 listed)
- ECOG performance status of 3 or more or if <16 years of age Lansky score of 50 or lower.
- Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to signing the consent
- Patients with fever or suspected minor infection should await resolution of symptoms before signing the consent
- Major anticipated illness or organ failure incompatible with survival from PBSC transplant
- Pregnant or breastfeeding
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 CD34 ReagentHaploidentical recipients will receive CD34-selected cells using Miltenyi CliniMACS(R) CD34+ cell selection kits. The target CD34+ cell dose is at least 10 x 106/kg, and the minimum CD34+ cell dose is 5 x 106/kg. All of the cells collected during the apheresis procedure will be given. The cells will be cryopreserved and stored until the day of transplant. | Device | 1, 2 |
Primary outcome
dichotomous positive/negative outcome where a positive response is defined by absence of graft rejection
Time frame: 5 years
The primary endpoint for each individual is a dichotomous positive/negative outcome where a positive response is defined by absence of graft rejection, and absence of severe acute GVHD (grade 3 and higher), or moderate to severe chronic GVHD evaluated 100 days post-transplant.
1 secondary outcome
Incidence of graft rejection defined as HbS >10% when donors have HbAA and HbS >50% when donors have sickle cell trait
Time frame: 5 years
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 26 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Courtney F Joseph, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
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 CliniMACS CD34 Reagent in people with Myeloid Chimerism, run by National Heart, Lung, and Blood Institute (NHLBI) 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 8 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: looking for participants now, as of the sponsor's last update on 26 Oct 2026. 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?
Contact Julia M Varga, R.N. ((301) 402-3595, julia.varga@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
dichotomous positive/negative outcome where a positive response is defined by absence of graft rejection (time frame: 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 26 Oct 2026.