Haploidentical Bone Marrow Transplantation in Sickle Cell Patients (BMTCTN1507)
Reduced Intensity Conditioning for Haploidentical Bone Marrow Transplantation in Patients With Symptomatic Sickle Cell Disease. (BMTCTN1507)
3 other identifiers
interventional
95
1 country
32
Brief 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). Based on their age and entry criteria patients are stratified into two groups: (1) children with severe SCD; and (2) adults with severe SCD.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Oct 2017
Longer than P75 for phase_2
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 24, 2017
CompletedFirst Posted
Study publicly available on registry
August 28, 2017
CompletedStudy Start
First participant enrolled
October 3, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 29, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 29, 2025
CompletedResults Posted
Study results publicly available
April 29, 2026
CompletedApril 29, 2026
April 1, 2026
7.3 years
August 24, 2017
January 28, 2026
April 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
2 years post-transplant
Secondary Outcomes (33)
Percentage of Participants With Two-Year Post-Transplant Overall Survival (OS)
2 years post-transplant
Number of Participants With Graft Failure
2 Years post-transplant
Percentage of Participants With Disease Recurrence Post-Transplant
1 year and 2 years post-transplant
Percentage of Participants With Neutrophil Recovery Post-Transplant
42 Days post-transplant
Percentage of Participants With Platelet Recovery Post-Transplant
60 Days, 100 Days post-transplant
- +28 more secondary outcomes
Other Outcomes (1)
Mean Follow-up Days Since Transplant
From transplant up to 2 years post-transplant
Study Arms (1)
Haploidentical Transplantation
EXPERIMENTALA conditioning regimen with Hydroxyurea, rabbit-ATG, Thiotepa, Fludarabine, Cyclophosphamide, Total Body Irradiation, and Mesna will be administered prior to Haploidentical Bone Marrow Transplantation.
Interventions
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.
HU will be given daily at 30mg/kg from Day -70 through Day -10.
Rabbit-ATG (rATG) will be given at 0.5mg/kg on Day -9, and at 2.0mg/kg on Day -8 and Day -7.
Thiotepa will be given at 10mg/kg on Day -7
Fludarabine will be given at 30mg/m2 from Day -6 to Day -2
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 Irradiation will be given at 200cGy on Day -1
Mesna will be given at 40mg/kg on Days +3 and +4
Eligibility Criteria
You may qualify if:
- 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:
- 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.
- Age 5.00 - 14.99 years at Segment A enrollment
- Participants with sickle cell anemiam disease (Hb SS or SĂŸÂ° 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.
- +15 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical College of Wisconsinlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Cancer Institute (NCI)collaborator
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- National Marrow Donor Programcollaborator
Study Sites (32)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
University of Colorado - Denver/Children's Hospital of Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
University of Florida College of Medicine
Gainesville, Florida, 32610, United States
Nicklaus Children's Hospital/University of Miami Children's Hospital
Miami, Florida, 33155, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
Riley Children's Hospital at IU Health
Indianapolis, Indiana, 46020, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
Helen Devos Children's at Spectrum Health
Grand Rapids, Michigan, 49503, United States
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104, United States
Washington University, St. Louis
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Roswell Park Cancer Center
Buffalo, New York, 14203, United States
Northwell Health/Monter Cancer Center
Lake Success, New York, 11042, United States
Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
University Hospitals of Cleveland/Case Western
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205-2696, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260, United States
Methodist Healthcare/West Cancer Center
Memphis, Tennessee, 38104, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Texas Children's Hospital (Baylor)
Houston, Texas, 77030, United States
University of Texas/MD Anderson Cancer Center
Houston, Texas, 77030, United States
Texas Transplant Institute
San Antonio, Texas, 78229, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
The Medical College of Wisconsin
Wauwatosa, Wisconsin, 53226, United States
Related Publications (3)
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.
PMID: 39998301RESULTKassim 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.
PMID: 39998298RESULTLeonard 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.
PMID: 36240296DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Company, LLC
Study Officials
- STUDY DIRECTOR
Mary Horowitz, MD
Center for International Blood and Marrow Transplant Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 24, 2017
First Posted
August 28, 2017
Study Start
October 3, 2017
Primary Completion
January 29, 2025
Study Completion
January 29, 2025
Last Updated
April 29, 2026
Results First Posted
April 29, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Within 6 months of official study closure at participating sites.
- Access Criteria
- Available to the public
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).