Severe Sickle Cell DiseasePhase 1/2FAM BMTNCT03128996
Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders
A Phase 1/2 study testing RIC regimen and GVHD prophylaxis regimen in people with Severe Sickle Cell Disease and Bone Marrow Failure Syndromes, run by Washington University School of Medicine at 4 sites in United States.
Trial summary
This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure. Read more about this study
- Who is it for?
- Ages 1 day to 21 years
- Conditions the study is for
- Severe Sickle Cell Disease, Bone Marrow Failure Syndromes, Metabolic Disorders
- What is being tested?
- RIC regimen and GVHD prophylaxis regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 4 sitesUnited States
- Study dates
- 20 Mar 2017to Apr 2033
- 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 1 day to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy
- For patients with sickle cell disease, must have one of the following severe manifestations:
- Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy
- Recurrent acute chest syndrome with significant respiratory compromise each time
- Sickle nephropathy
- Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity
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- Red cell alloimmunization with the need for chronic transfusions
- Recurrent osteonecrosis or multiple joint involvement from avascular necrosis
- Patients with sickle cell disease must have hemoglobin S < 30% within 30 days prior to beginning alemtuzumab
- Age </= 20.99 years at the time of enrollment
- Performance score >/= 50
- Left ventricular ejection fraction > 40% or left ventricular shortening fraction > 26% by echocardiogram
- DLCO > 40% (corrected for hemoglobin) or pulse oximetry with a baseline O2 saturation of >/= 90% on room air if too young to perform PFTs
- Serum creatinine </= 1.5x upper limit of normal for age and/or GFR > 70 mL/min/1.73m2
- Direct bilirubin < 2x upper limit of normal for age
- ALT and AST < 5x upper limit of normal for age
- Participants who have or are receiving >/= 8 packed red blood cell transfusions for >/= 1 year or >/= 20 packed red blood cell transfusions (lifetime cumulative) will undergo liver MRI for estimation of hepatic iron content.
- 1. Liver biopsy is indicated for hepatic iron content >/= 7mg Fe/mg liver dry weight by liver MRI. Histologic examination of the liver must document for the absence of cirrhosis, bridging fibrosis, and active hepatitis
- Female subjects of childbearing potential, must agree to practice 2 methods of contraception at the same time from the time of signing of informed consent through 12 months post transplant. Male subjects must agree to practice effective barrier contraception or practice true abstinence from the time of signing informed consent through 12 months post transplant.
- Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution's Human Studies Committee.
Who cannot join
- Patients who have an HLA-identical sibling who is able and willing to donate bone marrow
- Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis
- Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment
- Evidence of HIV infection or known HIV positive serology
- Patients who have received a previous stem cell transplant
- Patients who have received an investigational drug or device or off-label use of a drug or device within 3 months of enrollment
- Females who are pregnant or breast feeding
- Patients with active autoimmune disease (e.g. sarcoidosis, lupus, scleroderma)
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Troy Quigg, DO
Troy Quigg, DO
- Recruiting
Yale School of Medicine
New Haven, Connecticut, 06510
Lakshmanan Krishnamurti, MD
Lakshmanan Krishnamurti, MD
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Shalini Shenoy, MD, 314-454-6018, shalinishenoy@wustl.edu
Ian Snyder, BS, CCRP, 314-273-5953, ian.s@wustl.edu
- Recruiting
Nemours Children's Health
Wilmington, Delaware, 19803
Emi Caywood, MD, 800-416-4441
Emi Caywood, MD
About this study
Official title: A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders
This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.
Read the detailed description
Patients < 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan.
This will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.
- Conditions
- Severe Sickle Cell Disease, Bone Marrow Failure Syndromes, Metabolic Disorders, Immunologic Disorders, Hemoglobinopathies, Non-malignant Disorders
- Being tested
- RIC regimen, GVHD prophylaxis regimen
- Keywords
- Bone marrow transplant, Transplant, Transplantation, Reduced Intensity, Familial HLA mismatched
- Medical subject headings
- Anemia, Sickle Cell, Bone Marrow Failure Disorders, Metabolic Diseases, Immune System Diseases, Hemoglobinopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RIC regimenDrug
Also called Transplant Preparative Regimen, Transplant Conditioning Regimen
Days -60 to -21: hydroxyurea (30mg/kg/day po) >6hrs prior to 1st dose: alemtuzumab (3mg IV) Day -21: alemtuzumab (10mg IV or S/C) Day -20: alemtuzumab (15mg IV or S/C) (10mg if < 10kg) Day -19: alemtuzumab (20mg IV or S/C) (10mg if < 10kg) Days -8 to -4: fludarabine (30mg/m2/day IV) Day -4: thiotepa (8mg/kg IV) Day -3: melphalan (140mg/m2) Days -2 to -1: rest days/no therapy Day 0: bone marrow transplant
GVHD prophylaxis regimenDrug
Also called Graft versus Host Disease prophylaxis regimen
Day +3 to +4: cyclophosphamide (50mg/kg/day IV) Day +5: Start of tacrolimus \& Start of mycophenolate mofetil (MMF) Days +5, +14, +30, +60, +90: abatacept (IND) (10mg/kg/day IV) Day +90: rituximab (375mg/m2 IV once) Patients >/= 12 yrs - Days +120 to +180: abatacept (IND) monthly (10mg/kg/day IV) Patients >/= 12 yrs - Days +210 to +390: abatacept (IND) monthly (5mg/kg/day) Patients <12 yrs - Days +120 to +390: abatacept (IND) monthly (5mg/kg/day IV)
| Study group | Role | What they receive |
|---|---|---|
| RIC Prep Regimen & GVHD Prophylaxis | Experimental | Single arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen Receives: Drug: RIC regimen; Drug: GVHD prophylaxis regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Donor engraftment
as measured by chimerism
Measured: 100 days and 1 year post-transplant
Secondary outcomes (12)
Time to neutrophil engraftment
as measured by complete blood counts
Measured: 100 days post-transplant
Time to platelet engraftment
as measured by complete blood counts
Measured: 100 days post-transplant
Effect of BMT on pulmonary function
as measured by pulmonary function tests
Measured: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on hepatic function
as measured by laboratory evaluations
Measured: 90 days, 180 days, 1 year, and 2 years post-transplant
Effect of BMT on neurologic function
as measured by cognitive testing and quality of life surveys
Measured: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on cardiac function
as measured by echocardiograms
Measured: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on renal function
as measured by laboratory evaluations
Measured: 90 days, 180 days, 1 year, and 2 years post-transplant
Pharmacokinetics of alemtuzumab
as measured by maximum plasma concentration of alemtuzumab
Measured: days -19, day 0, day +15, and day +30
Pharmacokinetics of abatacept
as measured by maximum plasma concentration of abatacept
Measured: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
Incidence of acute graft-versus-host disease (GVHD)
as measured by protocol grading scale
Measured: 1 year post-transplant
Incidence of chronic graft-versus-host disease (GVHD)
as measured by protocol grading scale
Measured: 2 years post-transplant
Immune reconstitution
as measured by research laboratory evaluations
Measured: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2017
- Study start20 Mar 2017
- Primary completionApr 2028 (estimated)
- Study completionApr 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shalini Shenoy, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03128996
- Sponsor's protocol ID
- 201611172
- Acronym
- FAM BMT
- Status last verified
- May 2026
- First submitted
- 3 Apr 2017
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ngwube A, Shah N, Godder K, Jacobsohn D, Hulbert ML, Shenoy S. Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease. Blood Adv. 2020 Aug 25;4(16):3894-3899. doi: 10.1182/bloodadvances.2020002236.
PubMed 32813873
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders
- ClinicalTrials.gov ID
- NCT03128996
- Acronym / sponsor ID
- FAM BMT / 201611172
- Conditions
- Severe Sickle Cell Disease, Bone Marrow Failure Syndromes, Metabolic Disorders, Immunologic Disorders, Hemoglobinopathies, Non-malignant Disorders
- Keywords
- Bone marrow transplant, Transplant, Transplantation, Reduced Intensity, Familial HLA mismatched
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 20 Mar 2017 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2033 (estimated)
- First posted
- 26 Apr 2017 (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.
This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.
Detailed description
Patients < 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan.
This will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RIC Prep Regimen & GVHD Prophylaxis | Experimental | Drug: RIC regimen, Drug: GVHD prophylaxis regimenSingle arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen |
Who may qualify
- Ages
- 1 day to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy
- For patients with sickle cell disease, must have one of the following severe manifestations:
- Patients with sickle cell disease must have hemoglobin S < 30% within 30 days prior to beginning alemtuzumab
- Age </= 20.99 years at the time of enrollment
- Performance score >/= 50
Key exclusion criteria (8 listed)
- Patients who have an HLA-identical sibling who is able and willing to donate bone marrow
- Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis
- Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment
- Evidence of HIV infection or known HIV positive serology
- Patients who have received a previous stem cell transplant
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 |
|---|---|---|
| RIC regimenAlso: Transplant Preparative Regimen, Transplant Conditioning RegimenDays -60 to -21: hydroxyurea (30mg/kg/day po) >6hrs prior to 1st dose: alemtuzumab (3mg IV) Day -21: alemtuzumab (10mg IV or S/C) Day -20: alemtuzumab (15mg IV or S/C) (10mg if < 10kg) Day -19: alemtuzumab (20mg IV or S/C) (10mg if < 10kg) Days -8 to -4: fludarabine (30mg/m2/day IV) Day -4: thiotepa (8mg/kg IV) Day -3: melphalan (140mg/m2) Days -2 to -1: rest days/no therapy Day 0: bone marrow transplant | Drug | RIC Prep Regimen & GVHD Prophylaxis |
| GVHD prophylaxis regimenAlso: Graft versus Host Disease prophylaxis regimenDay +3 to +4: cyclophosphamide (50mg/kg/day IV) Day +5: Start of tacrolimus \& Start of mycophenolate mofetil (MMF) Days +5, +14, +30, +60, +90: abatacept (IND) (10mg/kg/day IV) Day +90: rituximab (375mg/m2 IV once) Patients >/= 12 yrs - Days +120 to +180: abatacept (IND) monthly (10mg/kg/day IV) Patients >/= 12 yrs - Days +210 to +390: abatacept (IND) monthly (5mg/kg/day) Patients <12 yrs - Days +120 to +390: abatacept (IND) monthly (5mg/kg/day IV) | Drug | RIC Prep Regimen & GVHD Prophylaxis |
Primary outcome
Donor engraftment
Time frame: 100 days and 1 year post-transplant
as measured by chimerism
12 secondary outcomes
Time to neutrophil engraftment
Time frame: 100 days post-transplant
Time to platelet engraftment
Time frame: 100 days post-transplant
Effect of BMT on pulmonary function
Time frame: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on hepatic function
Time frame: 90 days, 180 days, 1 year, and 2 years post-transplant
Effect of BMT on neurologic function
Time frame: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on cardiac function
Time frame: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on renal function
Time frame: 90 days, 180 days, 1 year, and 2 years post-transplant
Pharmacokinetics of alemtuzumab
Time frame: days -19, day 0, day +15, and day +30
Pharmacokinetics of abatacept
Time frame: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
Incidence of acute graft-versus-host disease (GVHD)
Time frame: 1 year post-transplant
Incidence of chronic graft-versus-host disease (GVHD)
Time frame: 2 years post-transplant
Immune reconstitution
Time frame: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
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 29 May 2026.
- Derived from this study: PubMed 32813873Ngwube A, Shah N, Godder K, Jacobsohn D, Hulbert ML, Shenoy S. Abatacept is effective as GVHD prophylaxis in unrelated donor stem cell transplantation for children with severe sickle cell disease. Blood Adv. 2020 Aug 25;4(16):3894-3899. doi: 10.1182/bloodadvances.2020002236.
- Individual participant dataSharing planned: No
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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.
Shalini Shenoy, MD principal investigator
Washington University School of Medicine
4 sites 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 RIC regimen and GVHD prophylaxis regimen in people with Severe Sickle Cell Disease and Bone Marrow Failure Syndromes, run by Washington University School of Medicine at 4 sites 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 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 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 Shalini Shenoy, MD (314-454-6018, shalinishenoy@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Donor engraftment (time frame: 100 days and 1 year post-transplant). 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 NCT03128996, 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 29 May 2026.