Sickle Cell DiseasePhase 2NCT03263559
Haploidentical Bone Marrow Transplantation in Sickle Cell Patients (BMTCTN1507)
A Phase 2 study testing Haploidentical Bone Marrow Transplantation, Hydroxyurea and Rabbit-ATG in people with Sickle Cell Disease, run by Medical College of Wisconsin at 32 sites in United States.
Trial summary
This is a Phase II, single arm, multi-center trial, designed to estimate the efficacy and toxicity of haploidentical bone marrow transplantation (BMT) in patients with sickle cell disease (SCD). Read more about this study
- Who is it for?
- Ages 5 to 45 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Haploidentical Bone Marrow Transplantation, Hydroxyurea and Rabbit-ATG
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 32 sitesUnited States
- Study dates
- 3 Oct 2017to 29 Jan 2025
- Phase
- Phase 2
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 5 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Adequate physical function as measured by all of the following:
- A Karnofsky/Lansky performance score of ≥ 60.
- Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA) scan.
- Pulmonary function: Pulse oximetry with a baseline O2 saturation of ≥ 85% and Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% (corrected for hemoglobin).
- Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and estimated or measured creatinine clearance ≥ 70 mL/min/1.73 m²
- Hepatic function:
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- Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory. Participants with hyperbilirubinemia as the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5x upper limit of normal as per local laboratory.
- Liver MRI using a validated methodology per institutional preference (T2* or R2* or by ferriscan [R2 MRI]) for estimation of hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions per year for ≥1 year or have received ≥20 packed red blood cell transfusions (lifetime cumulative). Participants who have hepatic iron content ≥ 10 mg Fe/g liver dry weight by liver MRI must have a Gastroenterology/hepatology consultation with liver biopsy and histological examination including documentation of the absence of cirrhosis, bridging fibrosis, and active hepatitis.
- Participants must be HLA typed at high resolution using DNA based typing at HLA-A, -B, -C, DRB1, and have available:
- An HLA haploidentical first degree relative donor (parents, siblings or half siblings, or children) with 2, 3, or 4 (out of 8) HLA-mismatches who is willing and able to donate bone marrow. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must be HLA identical for at least one antigen (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype, and typing of additional family members is not required. Confirmatory donor HLA typing must be completed < 100 days prior to Segment A enrollment
- Umbilical cord blood or peripheral blood stem cell donors will not be accepted.
- Inclusion Criteria for Stratum 1: Children Ages 5.00 - 14.99 years of age at enrollment
- Age 5.00 - 14.99 years at Segment A enrollment
- Participants with sickle cell anemiam disease (Hb SS or Sß° Thalassemia) who have one or more of the following:
- A neurological event resulting in focal neurologic deficits that lasted ≥ 24 hours (classical clinical definition of stroke, not requiring imaging studies of the brain) OR a focal neurological event resulting in abnormalities on T2-weighted or FLAIR images using a MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain), OR both.
- Abnormal transcranial Doppler (TCD) measurement with a timed average maximum mean velocity of at least 200 cm/sec in the terminal portion of the internal carotid or proximal portion of middle cerebral artery or if the imaging TCD method is used > 185 cm/sec plus evidence of intracranial vasculopathy.
- Silent Cerebral Infarct defined as an infarct-like lesion based on an MRI signal abnormality at least 3 mm in one dimension and visible in two planes on FLAIR or T2-weighted images (or similar image with 3D imaging) and documented neurological examination performed by a neurologist demonstrating the participant has a normal neurologic examination or an abnormality on examination that could not be explained by the location of the brain lesion(s).
- Acute severe vaso-occlusive pain episodes requiring hospitalization and recalcitrant to maximum medical therapy. Episodes of pain to be adjudicated by selected committee.
- One acute chest syndrome episode resulting in intensive care admission requiring non-mechanical ventilatory support: simple nasal cannula, face mask that requires oxygen content (venti mask, non-rebreather), simple nasal cannula, face mask O2(e.g. ventimask, rebreather), CPAP, SiPAP, BiPAP, high flow nasal cannula (HFNC) or invasive mechanical ventilatory support (delivered by ETT or trach).
- Right heart catheterization confirmed pulmonary artery pressure >25 mmHG or mean pulmonary vascular resistance 206(57-421) dyn·s·cm-5
- Essential hypertension on antihypertensive medications >95% upper limit of normal age (as defined according to the American Academy of Pediatrics)
- Recurrent priapism (episodes lasting at least 4 hours at least twice in the last 12 months or 3 times in the last 24 months) recalcitrant to medical treatment or unable to use hydroxyurea due to SCD phenotype with the approval of the adjudication committee
- Inclusion Criteria for Stratum 2: Adults Ages 15.00 - 45.99 at enrollment
- Participants with sickle cell anemia (Hb SS or Sß° Thalassemia) who are 15.00 - 45.99 years of age at enrollment AND who have one or more of the following:
- Age 15.00 - 45.99 years at Segment A enrollment
- Participants with sickle cell anemia (Hb SS or Sß° Thalassemia) who have one or more of the following:
- A neurological event resulting in focal neurologic deficits that lasted ≥ 24 hours (classical clinical definition of stroke, not requiring imaging studies of the brain) OR a focal neurological event resulting in abnormalities on T2-weighted or FLAIR images using a MRI scan, indicative of an acute infarct, with no other reasonable medical explanation (definition of a stroke supported with MRI imaging scans of the brain), OR both.
- History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea);
- History of three or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea); painful episodes related to priapism, osteonecrosis or any sickle-related complication are acceptable;
- Administration of regular RBC transfusion therapy, defined as receiving ≥8 packed red blood cell transfusions per year for ≥1 year in the 12 months before enrollment to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome);
- An echocardiographic finding of tricuspid valve regurgitant jet velocity (TRJV) ≥ 2.7 m/sec.
Who cannot join
- Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donor are not excluded.
- Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- Evidence of HIV infection or known HIV positive serology.
- Participants who have received a previous hematopoetic cell transplant (HCT).
- Participants who have had an Encephaloduroarteriosynangiosis (EDAS) procedure in the 6 months prior to enrollment
- Participants who have received a prior solid organ transplant
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- Participants who have participated in another clinical trial in which the patient received an investigational or off-label use of a drug or device within 3 months of enrollment.
- Females who are pregnant or breastfeeding.
- Participants with clinically significant, uncontrolled autoimmune disease, requiring active medical management (immunosuppressive therapy or chemotherapy), which, in the judgment of the local Principal Investigator, indicates that the patient could not tolerate transplantation.
- Females of child bearing potential (to include all female participants > 10 years of age, unless postmenopausal for a minimum of 1 year before the time of consent or surgically sterilized), who do not agree to practice two (2) effective methods of contraception at the same time, or do not agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject, from the time of signing of informed consent through 12 months post-transplant.
- Males (even if surgical sterilized) who do not agree to practice effective barrier contraception, or who do not agree to practice true abstinence from the time of signing informed consent through 12 months post-transplant.
- Presence of anti-donor specific HLA antibodies. HLA antibody presence and specificity will be determined by solid phase immunoassays. An anti-donor specific HLA antibody will be considered positive when the mean fluorescence intensity (MFI) is higher than the cut-off defined by each institution. Recommended cut-off values are MFI >1000 for donor specific antibody to HLA-A, -B, and DRB1 and MFI >2000 for HLA-C, DQB1 and DPB1. This must be measured before the final donor selection, and < 100 days before enrollment in Segment A (preferably < 30 days before Segment A enrollment). If MFI >1000 for donor specific antibody to HLA-A, -B, DRB1 and/or MFI >2000 for HLA-C, DQB1 and DPB1, documentation must be submitted to the DCC coordinator for review and approval by a Protocol Chair and/or Protocol Officer prior to enrollment
Trial locations and contacts
32 sites in 1 country.
32 sites in 1 country
United States32 sites
Northside Hospital
Atlanta, Georgia, 30342
University of Colorado - Denver/Children's Hospital of Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Roswell Park Cancer Center
Buffalo, New York, 14203
Levine Children's Hospital
Charlotte, North Carolina, 28203
University Hospitals of Cleveland/Case Western
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Nationwide Children's Hospital
Columbus, Ohio, 43205-2696
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27705
University of Florida College of Medicine
Gainesville, Florida, 32610
Helen Devos Children's at Spectrum Health
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Texas Children's Hospital (Baylor)
Houston, Texas, 77030
University of Texas/MD Anderson Cancer Center
Houston, Texas, 77030
Riley Children's Hospital at IU Health
Indianapolis, Indiana, 46020
Indiana University Medical Center
Indianapolis, Indiana, 46202
Northwell Health/Monter Cancer Center
Lake Success, New York, 11042
Methodist Healthcare/West Cancer Center
Memphis, Tennessee, 38104
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Nicklaus Children's Hospital/University of Miami Children's Hospital
Miami, Florida, 33155
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
Texas Transplant Institute
San Antonio, Texas, 78229
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University, St. Louis
St Louis, Missouri, 63110
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Children's National Medical Center
Washington D.C., District of Columbia, 20010
The Medical College of Wisconsin
Wauwatosa, Wisconsin, 53226
About this study
Official title: Reduced Intensity Conditioning for Haploidentical Bone Marrow Transplantation in Patients With Symptomatic Sickle Cell Disease. (BMTCTN1507)
This is a Phase II, single arm, multi-center trial, designed to estimate the efficacy and toxicity of haploidentical bone marrow transplantation (BMT) in patients with sickle cell disease (SCD). Based on their age and entry criteria patients are stratified into two groups: (1) children with severe SCD; and (2) adults with severe SCD.
Read the detailed description
This study is designed as a Phase II multi-center trial to determine the feasibility of achieving a high rate of event-free survival (EFS) at 2 years post transplant using pre-conditioning hydroxyurea (HU) with a conditioning regimen that consists of a combination of Thymoglobulin/Cyclophosphamide/Fludarabine/Thiotepa with post-grafting high-dose cyclophosphamide in patients with severe SCD who have HLA-haploidentical donors. EFS is defined as survival without a qualifying event. This is a single arm study in which participants will be enrolled into one of two strata. The first stratum will be restricted to children who have stroke and 40 children will be enrolled in this stratum. The second stratum will consist of adult patients with severe sickle cell disease and 40 participants will be enrolled in this stratum.
- Conditions
- Sickle Cell Disease
- Being tested
- Haploidentical Bone Marrow Transplantation, Hydroxyurea, Rabbit-ATG, Thiotepa, Fludarabine
- Keywords
- Reduced Intensity Conditioning, Haploidentical, Bone Marrow, Transplant, Sickle Cell Disease
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haploidentical Bone Marrow TransplantationProcedure or surgery
Eligible patients with a first degree Human Leukocyte Antigen (HLA)- haploidentical donor will undergo Haploidentical bone marrow transplantation at Day 0 with non T-cell depleted bone marrow. For Graft-vs-Host Disease (GVHD) prophylaxis, patients will be given sirolimus and mycophenolate mofetil beginning on Day +5.
HydroxyureaDrug
Also called Hydrea, Droxia
HU will be given daily at 30mg/kg from Day -70 through Day -10.
Rabbit-ATGDrug
Also called Thymoglobulin
Rabbit-ATG (rATG) will be given at 0.5mg/kg on Day -9, and at 2.0mg/kg on Day -8 and Day -7.
ThiotepaDrug
Also called Chemo
Thiotepa will be given at 10mg/kg on Day -7
FludarabineDrug
Also called Fludara
Fludarabine will be given at 30mg/m2 from Day -6 to Day -2
CyclophosphamideDrug
Also called Cytoxan®
Cyclophosphamide will be given at 14.5mg/kg on Day -6 and Day -5, and at 50 mg/kg on Days +3 and +4.
Total Body IrradiationRadiation
Also called TBI
Total Body Irradiation will be given at 200cGy on Day -1
MesnaDrug
Also called Mesnex
Mesna will be given at 40mg/kg on Days +3 and +4
| Study group | Role | What they receive |
|---|---|---|
| Haploidentical Transplantation | Experimental | A conditioning regimen with Hydroxyurea, rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide, Total Body Irradiation, and Mesna will be administered prior to Haploidentical Bone Marrow Transplantation. Receives: Procedure: Haploidentical Bone Marrow Transplantation; Drug: Hydroxyurea; Drug: Rabbit-ATG; Drug: Thiotepa; Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Drug: Mesna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Two-Year Post-Transplant Event Free Survival (EFS)
EFS is defined as survival without a qualifying event from transplant. Primary graft failure (PGF), secondary graft failure (SGF), second infusion of hematopoietic cells, or death from any cause will count as events for this endpoint. This endpoint was adjudicated by an Endpoint Review Committee.
PGF is lack of engraftment on or before Day 42 post-transplant. Engraftment is defined as having greater than or equal to 5% donor cells post-transplant, from any molecular chimerism assessment (e.g., unsorted, myeloid, or T-cell) on a peripheral blood or bone marrow aspirate sample. SGF is defined as < 5% donor whole blood or myeloid chimerism in peripheral blood or bone marrow beyond day +42 post-transplant in patients with prior documentation of hematopoietic recovery with >5% donor cells by day +42 post-transplant. Infusion of a second stem cell product will be considered graft rejection, and counted toward primary or, depending on timing of the second infusion, secondary graft rejection
Measured: 2 years post-transplant
Secondary outcomes (33)
Percentage of Participants With Two-Year Post-Transplant Overall Survival (OS)
Death from any cause will be the event and patients will be censored at the date of last contact or two years post-transplant, whichever comes first.
Measured: 2 years post-transplant
Number of Participants With Graft Failure
Primary Graft Failure (PGF) is lack of engraftment on or before Day 42 post-transplant. Engraftment is defined as having greater than or equal to 5% donor cells post-transplant, from any molecular chimerism assessment (e.g., unsorted, myeloid, or T-cell) on a peripheral blood or bone marrow aspirate sample. Secondary Graft Failure (SGF) is defined as < 5% donor whole blood or myeloid chimerism in peripheral blood or bone marrow beyond day +42 post-transplant in patients with prior documentation of hematopoietic recovery with >5% donor cells by day +42 post-transplant. Infusion of a second stem cell product will be considered graft rejection, and counted toward primary or, depending on timing of the second infusion, secondary graft rejection.
Measured: 2 Years post-transplant
Percentage of Participants With Disease Recurrence Post-Transplant
Disease Recurrence is defined as primary graft failure, secondary graft failure, or sickle hemoglobin (HbS) > 70% within 2 years post-transplant. Cumulative Incidence of Disease Recurrence was estimated with a 95% confidence interval using the Aalen-Johansen estimator with death prior to disease recurrence treated as a competing risk. This endpoint was adjudicated by an Endpoint Review Committee.
Measured: 1 year and 2 years post-transplant
Percentage of Participants With Neutrophil Recovery Post-Transplant
Neutrophil recovery is defined as the first of 3 measurements on different days when the patient has an absolute neutrophil count of ≥500/μL after conditioning. The incidence of neutrophil recovery from transplant will be estimated using the cumulative incidence function with a 95% confidence interval using the Aalen-Johansen estimator with death or second transplant without neutrophil recovery as a competing risk.
Measured: 42 Days post-transplant
Percentage of Participants With Platelet Recovery Post-Transplant
Platelet recovery is defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count > 50,000/μL AND did not receive a platelet transfusion in the previous 7 days. The incidence of platelet recovery from transplant will be estimated using the cumulative incidence function with a 95% confidence interval using the Aalen-Johansen estimator with death or second transplant without platelet recovery as a competing risk.
Measured: 60 Days, 100 Days post-transplant
Mean Percentage of Donor Chimerism Post-Transplant
A point estimate and confidence interval will be provided for the mean percent donor chimerism at the time points specified including Day 28, Day 100, Day 180, 1 year, and 2 years post-transplant. For each participant's visit with multiple chimerism sources recorded, donor percentage is determined by taking the first non-missing chimerism percentage in the following order of sources: marrow, blood, myeloid, and t-cell.
Measured: Days 28, 100, and 180 and at 1 and 2 years post-transplant
Percentage of Participants by Donor Chimerism Category Post-Transplant
At Day 28, Day 100, Day 180, 1 year and 2 years post-transplant, the proportions with low chimerism (<5%), mixed chimerism (5-95%), or full chimerism (>95%) will be tabulated and described. For each participant's visit with multiple chimerism sources recorded, donor percentage is determined by taking the first non-missing chimerism percentage in the following order of sources: marrow, blood, myeloid, and t-cell.
Measured: Days 28, 100, and 180 and at 1 and 2 years post-transplant
Number of Participants by Maximum Acute GVHD Grade Post-Transplant
Acute GVHD was graded according to Consensus Criteria with higher grade indicating worse outcomes. Grade I aGVHD is defined as stage 1-2 skin rash and no liver or GI involvement. Grade II is stage 3 skin rash, or stage 1 liver involvement, or stage 1 GI involvement. Grade III is stage 0-3 skin rash, with stage 2-3 liver involvement, or stage 2-3 GI involvement. Grade IV is stage 4 skin rash, liver, or GI involvement. Maximum grade is defined as the maximum grade of acute GVHD (0-IV) that a participant experiences by Day 100 post-transplant.
Measured: 100 Days post-transplant
Percentage of Participants With Acute GVHD Post-Transplant
Acute GVHD was graded according to Consensus Criteria with higher grade indicating worse outcomes. Grade I aGVHD is defined as stage 1-2 skin rash and no liver or GI involvement. Grade II is stage 3 skin rash, or stage 1 liver involvement, or stage 1 GI involvement. Grade III is stage 0-3 skin rash, with stage 2-3 liver involvement, or stage 2-3 GI involvement. Grade IV is stage 4 skin rash, liver, or GI involvement. The cumulative incidence of acute GVHD grade II-IV and III-IV at Day 100 was estimated using the Aalen-Johansen estimator with 95% confidence intervals, treating death prior to aGVHD as a competing event. Time to aGVHD is defined as time from transplant until onset of grades II-IV and III-IV aGVHD, respectively.
Measured: 100 Days post-transplant
Number of Participants by Maximum Chronic GVHD Severity Post-Transplant
Chronic GVHD is based on NIH Consensus Criteria (2014 NIH Consensus Criteria) and includes mild, moderate and severe chronic GVHD. Skin/hair, ocular, oral, pulmonary, gastrointestinal, hepatic, genitourinary, musculoskeletal, and hematologic systems were scored on a 0-3 scale to reflect degree of cGVHD involvement. Maximum grade is defined as the maximum grade of chronic GVHD (mild, moderate, or severe) that a participant experiences by 2 years post-transplant.
Measured: 2 Years post-transplant
Percentage of Participants With Chronic GVHD Post-Transplant
Percentage of participants with chronic GVHD (cGVHD) at will be estimated with 95% confidence intervals for each treatment group using the cumulative incidence estimate with the complementary log-log transformation, treating death prior to cGVHD as a competing event. Chronic GVHD is based on NIH Consensus Criteria (2014 NIH Consensus Criteria) and includes mild, moderate and severe chronic GVHD. Skin/hair, ocular, oral, pulmonary, gastrointestinal, hepatic, genitourinary, musculoskeletal, and hematologic systems were scored on a 0-3 scale to reflect degree of cGVHD involvement. This endpoint considers any cGVHD onset.
Measured: 6 months, 1 year, 2 years post-transplant
Number of Participants With Complications and Events Post-Transplant
The number of participants experiencing the following complications and events will be tabulated at baseline, 1 year and 2 years post-transplant: Idiopathic pneumonia syndrome (IPS), Veno-occlusive disease (VOD), Various Central Nervous System (CNS) toxicities, Stroke, participants on immunosuppression for GVHD, and significant infections reported (any bacterial/fungal sepsis, Cytomegalovirus (CMV) reactivation with/without clinical disease, adenovirus, Epstein-Barr Virus (EBV)).
Measured: Baseline, 1 year, and 2 years post-transplant
Number of Participants With Sickle Cell Disease Events of Special Interest Post-Transplant
Participants will be followed for the entire 2 year duration of their time on study for the recurrence of Sickle Cell Disease (SCD) related complications. These SCD related complications are referred to as SCD events of special interest (SCD-EOSI) and will be summarized with frequency. These SCD-EOSI include: pulmonary hypertension, new onset of significant cerebrovascular event, renal function compromise, new onset of avascular necrosis of hip or shoulder, new onset of leg ulceration, new onset of acute chest syndrome, and new onset of painful vaso-occlusive crisis requiring hospitalization or parenteral opioid drug in the outpatient setting.
Measured: Baseline, 6 months, 1 year, 18 months, and 2 Years post-transplant
Summary of Hematological Outcomes in Percentages
Hematological Outcomes will be summarized with mean and standard deviation at various timepoints. Depending on the measurement, "baseline" could be pre-hydroxyurea conditioning (day -70 pre-transplant) and/or pre-thymoglobulin (day -7 pre-transplant). Measures include: hemoglobin (Hgb) %, reticulocyte count %, and hemoglobin S level %.
Measured: Baseline, Day 28, Day 100, 6 months, 1, and 2 years post-transplant
Summary of Glomerular Filtration Rate (GFR)
Renal Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-thymoglobulin (day -7 pre-transplant). Measures include: GFR (mL/min/1.73m2) and Estimated GFR. Estimated GFR is computed using the CKD-EPI Creatinine Equation 2021 for Adults and the Bedside Schwartz 2009 equation for Pediatrics.
Measured: Baseline, 1, and 2 years post-transplant
Summary of Lung Function in Liters
Lung Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant). Measures include: FEV1 (L), FVC (L), and TLC (L). All values in this table were reported by study site.
Measured: Baseline, 1, and 2 years post-transplant
Summary of Cardiac Function
Cardiac Function is measured through tricuspid regurgitant jet velocity (TRJV). It will be summarized with mean and standard deviation at Baseline, 1, and 2 years post-transplant. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant).
Measured: Baseline, 1, and 2 years post-transplant
Summary of Six Minute Walk Distance
Six Minute Walk Distance is measured in meters to assess how far a participant can walk in 6 minutes. It will be summarized with mean and standard deviation at Baseline, 1, and 2 years post-transplant. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant). Change from baseline will also be provided at the 1 and 2 years post-transplant visit.
Measured: Baseline, 1, and 2 years post-transplant
Mean Patient Reported Quality of Life (QoL) Score
Health-Related Quality of Life (QoL) assessed using the NIH's PROMIS short forms administered to English- and Spanish-speaking patients in the adult stratum. Questions about fatigue (short form 8a), pain interference (short form 8a), and pain intensity (short form 3a) are asked regarding the degree of difficulty in performing activities of daily living such as housework, social activities, and day to day activities. It is scored from 0 to 10 and converted to a standardized T-score with mean 50 and standard deviation 10. A higher T-score represents worse fatigue, pain interfering with more daily activities, and worse pain intensity.
Measured: Baseline, 1, and 2 years post-transplant
Mean Patient Reported Pain Intensity Score From Pain Diary
Subjects who speak English and are 15 years or older will be asked to use a web-based diary to report pain intensity on a scale from 0 (no pain) to 10 (worst pain). Subject pain intensity score is reported as an aggregate of several AM and PM scores at Baseline, one year, and two years post-transplant timepoints.
Measured: Baseline, 1, and 2 years post-transplant
Number of Participants by Cause of Death
Cause of Death is tabulated by age strata. Deaths among participants who were not transplanted are included.
Measured: From Enrollment to 2 Years post-transplant
Number of Participants by Maximum Grade of Infection
Number of participants who reported the Maximum Infection Severity of Grade 2 and Grade 3. Only grade 2 and grade 3 infections occurring post transplantation were reported on the study. Grade 2 and grade 3 infections are defined by the BMT CTN Technical MOP. Higher infection grade indicates worse infection severity. The infection grading criteria are published online (https://bmtctn.net/administrative-manual-procedures-moppolicy-guidelines). Severity of grade 1, 2 and 3 are described for bacterial, fungal, viral, parasitic, and nonmicrobiological infections. For example, grade 2 fungal infections are defined as candida esophagitis, or proven or probably fungal sinusistis confirmed radiologically without orbital, brain or bone involvement. Grade 3 fungal infections are defined as Fungemia including candidemia, Proven or probably invasive fungal infections, Disseminated infections with histoplasmosis, blastomycosis, coccidiomycosis, or Cryptococcus, or Pneumocystis jiroveci pneumonia.
Measured: From Transplant to 2 Years post-transplant
Frequencies of Infections Categorized by Infection Type
The number of systemic infections is reported. Infections are categorized by infection type. A participant can report multiple types of infections, so the categories are not mutually exclusive for participants. All grade 2 and grade 3 infections, as defined by the BMT CTN Technical MOP, occurring post transplantation were reported on the study.
Measured: From Transplant to 2 Years post-transplant
Frequency of Hospital Readmissions by Cause
Participants could be readmitted to a hospital for many reasons during follow-up. The causes of each readmission are tabulated by age strata. The protocol-specified scheduled transplant hospitalization is not included in this table.
Measured: From Transplant to 2 Years post-transplant
Summary of Lactate Dehydrogenase (LDH)
Hematological Outcomes will be summarized with mean and standard deviation at various post-transplant timepoints. Measures in this table include: LDH (U/L)
Measured: Day 28, Day 100, 6 months, 1, and 2 years post-transplant
Summary of Bilirubin
Hematological Outcomes will be summarized with mean and standard deviation at various timepoints. Baseline timepoint is pre-thymoglobulin (day -7 pre-transplant). Measures in this table include: Bilirubin (mg/dL)
Measured: Baseline, Day 28, Day 100, 6 months, 1, and 2 years post-transplant
Summary of Serum Ferritin
Hematological Outcomes will be summarized with mean and standard deviation at various timepoints. Baseline refers to pre-thymoglobulin (day -7 pre-transplant). Measures in this table include: Serum Ferritin Level (ng/dL)
Measured: Baseline pre-thymoglobulin visit (day -7 pre-transplant)
Summary of Creatinine Clearance
Renal Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-thymoglobulin (day -7 pre-transplant). Measures include: Creatinine Clearance (mL/min).
Measured: Baseline, 1, and 2 years post-transplant
Summary of Urine Albumin Creatine Ratio
Renal Function Outcomes will be summarized with mean and standard deviation at various timepoints. Measures include: Urine Albumin Creatine Ratio (mg/g).
Measured: 1 and 2 years post-transplant
Summary of Lung Function Percent Predicted
Lung Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant). Measures include: FEV1 (percent predicted), FVC (percent predicted), FEV1/FVC (percent predicted), and TLC (percent predicted). All values in this table, including percent predicted, were reported by study site.
Measured: Baseline, 1, and 2 years post-transplant
Summary of Lung Function Ratio of Liters
Lung Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant). Measures include: FEV1/FVC (ratio of Liters). All values in this table were reported by study site.
Measured: Baseline, 1, and 2 years post-transplant
Summary of Lung Function Percentages of Lab Measure
Lung Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant). Measures include: DLCO (%) and Oxygen Saturation (%). All values in this table were reported by study site.
Measured: Baseline, 1, and 2 years post-transplant
Summary of Lung Function Ratio of Percent Predicted
Lung Function Outcomes will be summarized with mean and standard deviation at various timepoints. "Baseline" refers to pre-hydroxyurea (day -70 pre-transplant). Measures include: FEV1/FVC (ratio of percent predicted). All values in this table were reported by study site.
Measured: Baseline, 1, 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 posted28 Aug 2017
- Study start3 Oct 2017
- Primary completion29 Jan 2025
- Study completion29 Jan 2025
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 (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies 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
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI), Blood and Marrow Transplant Clinical Trials Network, National Marrow Donor Program
- Responsible party
- Sponsor
- Investigators
- Mary Horowitz, MD, Study director, Center for International Blood and Marrow Transplant Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03263559
- Sponsor's protocol ID
- BMTCTN1507
- Other IDs
- 2U10HL069294-11, 5U24CA076518
- Status last verified
- Jun 2026
- First submitted
- 24 Aug 2017
- Last updated
- 8 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).
Publications
Hong S, Horwitz ME. Cures for Sickle Cell Abound - How about Access? NEJM Evid. 2025 Mar;4(3):EVIDe2400428. doi: 10.1056/EVIDe2400428. Epub 2025 Feb 25. No abstract available.
PubMed 39998301Kassim AA, Walters MC, Eapen M, Smith M, Logan BR, Solh M, McKinney C, Nieder M, Ross M, Kent M, Abusin GA, Mallhi K, Silva JG, Shaughnessy P, Kanter J, Haines H, Farah R, Khaled YA, Ritzau N, Mendizabal A, Abraham A, Bollard C, Cooke K, de la Fuente J, Hanna R, Horowitz MM, Jordan LC, Bakshi N, Krishnamurti L, Leifer E, Mahadeo KM, Shenoy S, Jones RJ, DeBaun MR, Brodsky RA. Haploidentical Bone Marrow Transplantation for Sickle Cell Disease. NEJM Evid. 2025 Mar;4(3):EVIDoa2400192. doi: 10.1056/EVIDoa2400192. Epub 2025 Feb 25.
PubMed 39998298Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.
PubMed 36240296