- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00745420
Evaluating the Safety and Effectiveness of Bone Marrow Transplants in Children With Sickle Cell Disease (BMT CTN 0601) (SCURT)
Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children With Severe Sickle Cell Disease (BMT CTN #0601)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, also called "sickle cell crises." SCD is caused by an abnormal type of hemoglobin, which is a protein inside red blood cells that carries oxygen to vital organs, such as the brain, heart, lungs, and kidneys. Defective hemoglobin damages red blood cells. The damaged cells, in turn, can block blood flow in vessels and block oxygen and nutrients from reaching organs. For people with severe forms of SCD, one treatment option is a bone marrow transplant, which may correct the abnormal blood cell production problem. In most cases, bone marrow transplants are performed in people who have a healthy sibling with the same tissue type. If people do not have a sibling with the same tissue type, it is possible for them to receive a blood stem cell transplant from an unrelated donor through bone marrow transplant .
Traditionally, people with SCD who are undergoing a bone marrow transplant receive high doses of chemotherapy and medications before the transplant as part of the conditioning regimen to prepare their immune system to accept the donor cells. Participants will experience fewer side effects with a reduced intensity conditioning regimen than with a more intense conditioning regimen. The purpose of this study is to determine the safety and effectiveness of blood stem cell transplants, using bone marrow from unrelated donors, in children with severe SCD who receive a reduced intensity conditioning regimen before the transplant. Specifically, researchers will evaluate whether the reduced intensity conditioning regimen is successful in allowing donor cells to settle and grow successfully, in preventing the production of SCD-damaged red blood cells, and in limiting SCD-related organ damage.
This study will enroll children with severe SCD who lack a sibling with the same tissue type who can serve as their donor. Participants will attend a study visit prior to the transplant to undergo a blood collection, neurocognitive testing to measure learning and brain function, and magnetic resonance angiogram (MRA) and magnetic resonance imaging (MRI) scans. Questionnaires to assess quality of life will also be completed. Twenty-two days before the transplant, participants will begin receiving a reduced intensity conditioning regimen of chemotherapy and medications to prepare them for the transplant. Eight days before the transplant, participants will be admitted to the hospital and will continue the conditioning regimen. Participants will then receive the bone marrow transplant. After the transplant, participants will receive immunosuppression medications for at least 6 months to prevent graft-versus-host disease (GVHD), which may occur if the immune cells from the donated bone marrow attacks the body of the recipient. One week after the transplant, participants will receive granulocyte-colony-stimulating factor (G-CSF), which is a natural protein that increases the white blood cell count and helps protect the body against infections. Participants will receive G-CSF until their white blood cell level is normal again. Participants will remain in the hospital and be closely monitored for signs of infection or other complications until study researchers feel it is safe for them to return home.
After leaving the hospital, participants will attend study visits weekly during Weeks 1 to 8, at Day 60, weekly during Weeks 9 to 14, at Day 100, at Month 6, and at Years 1 and 2. At all study visits, a blood collection, medical history review, and physical exam will occur. In addition, at Day 100, Month 6, and Years 1 and 2, questionnaires to assess quality of life will be completed. At select visits the following procedures will also occur: lung function testing, heart function testing, MRA and MRI scans, and neurocognitive testing.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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Florida
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Miami, Florida, United States, 33136
- University of Miami
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Georgia
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Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta
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Illinois
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Chicago, Illinois, United States, 60614
- Ann & Robert H. Lurie Children's Hospital of Chicago
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Louisiana
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New Orleans, Louisiana, United States, 70118
- Children's Hospital of New Orleans/LSUMC CCOP
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Michigan
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Ann Arbor, Michigan, United States, 48105
- University of Michigan Medical Center
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Mississippi
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Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
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Missouri
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Kansas City, Missouri, United States, 64108
- Children's Mercy Hospital and Clinics
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Saint Louis, Missouri, United States, 63110
- Washington University, St. Louis Children's Hospital
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New York
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New Hyde Park, New York, United States, 11040
- Cohen Children's Hospital
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New York, New York, United States, 10032
- Columbia University Medical Center
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North Carolina
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Chapel Hill, North Carolina, United States, 27599
- University of North Carolina Hospital at Chapel Hill
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals of Cleveland
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- Children's Hospital of Pittsburgh
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South Carolina
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Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
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Texas
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Houston, Texas, United States, 77030
- Baylor College of Medicine/The Methodist Hospital
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Virginia
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Richmond, Virginia, United States, 23298
- Virginia Commonwealth University
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Wisconsin
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Milwaukee, Wisconsin, United States, 53211
- Medical College of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
SCD (genotype hemoglobin SS disease [Hb SS], genotype hemoglobin SC disease [HbSC],sickle ß°[Sß°] thalassemia, or sickle ß^+[Sß^+]thalassemia) with one or more of the following:
- Patients must have symptomatic SCD (genotype Hb SS, Hb SC, Sß° thalassemia or Sß+ thalassemia), AND have 1 or more of the following clinical complications:(i) Clinically significant neurologic event (stroke) or any neurologic deficit lasting more than 24 hours that is accompanied by an infarct on cerebral MRI; OR (ii) patients who have a Transcranial Doppler (TCD) velocity that exceeds 200 cm/sec by the non-imaging technique (or TCD measurement greater than 185 cm/sec by the imaging technique) measured at a minimum of 2 separate occasions one month or more apart; OR,
- Minimum of two episodes of acute chest syndrome in the 2 years before study entry, defined as new pulmonary alveolar consolidation involving at least one complete lung segment (associated with acute symptoms including fever, chest pain, tachypnea, wheezing, rales, or cough that is not attributed to asthma or bronchiolitis) despite adequate supportive care measures
- History of 3 or more severe pain events per year in the 2 years before study entry
- Lansky/Karnofsky performance score greater than or equal to 40
- Patients must have an unrelated adult bone marrow donor who is Human Leukocyte Antigen (HLA)-matched at 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
- Patients with adequate physical function: a)Cardiac: Left ventricular ejection fraction (LVEF) greater than 40%, or LV shortening fraction greater than 26%; b) Pulmonary: Pulse oxymetry with a baseline O2 saturation of greater than or equal to 85% is required for all patients, Carbon Monoxide Diffusing Capacity (DLCO) greater than 40% (corrected for hemoglobin) for patients in whom pulmonary function testing can be performed; c) Renal: Serum creatinine less than or equal to 1.5 x upper limit of normal for age and glomerular filtration rate (GFR) greater than 100 mL/min/1.73 m. For patients older than or equal to 16 years of age, GFR should be greater than 70 mL/min/1.73 m^2; d) Hepatic: Serum conjugated (direct) bilirubin less than 2x upper limit of normal for age as per local laboratory; alanine transaminase (ALT) and aspartate transaminase (AST) less than 5 times upper limit of normal as per local laboratory.
- If the patient has been receiving chronic transfusion therapy for more than or equal to 1 year AND has clinical evidence of iron overload (serum ferritin level of greater than 1000 ng/ml), a liver biopsy shall be obtained within 90 days of starting conditioning therapy (alemtuzumab). Histologic exam of the liver must document absence of bridging fibrosis or cirrhosis of the liver. In other cases, a liver biopsy is optional.
- Hemoglobin S (Hb S) level less than or equal to 45%, seven days prior to initiation of alemtuzumab
Exclusion Criteria:
- Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen
- Pregnant or breastfeeding
- Patients with 8/8 HLA-matched family donors able to donate
- Seropositivity for HIV
- Prior allogeneic marrow or stem cell transplant
- Iron chelation must be discontinued more than or equal to 48 hours before initiating the conditioning regimen
- Hydroxyurea (if receiving this therapy) must be discontinued more than or equal to 48 hours before initiating the conditioning regimen
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Hematopoietic Stem Cell Transplantation
Bone Marrow Transplant with GVHD Prophylaxis Regimen
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The stem cell transplant preparative regimen is listed below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Event-Free Survival (EFS)
Time Frame: 2 years
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EFS is defined as percentage of participants that have not had an event.
Primary or secondary graft rejection, disease recurrence, or death will count as events for this endpoint.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Overall Survival (OS)
Time Frame: 2 years
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OS is defined as the percentage of participants that have not died.
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2 years
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Neutrophil and Platelet Recovery
Time Frame: Up to 100 days
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Time to neutrophil recovery is defined as the time of the first of three measurements on consecutive days where the patient has an absolute neutrophil count of >= 500/uL following conditioning regimen induced nadir.
Time to platelet recovery is defined as the time of the first of three measurements on consecutive days where the patient has achieved a platelet count > 50,000/uL and is platelet transfusion independent for a minimum of seven days following conditioning regimen induced nadir.
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Up to 100 days
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Graft Rejection
Time Frame: 1 year
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Primary graft rejection is defined as the presence of less than 20% donor cells as assessed by peripheral blood or bone marrow chimerism assays on or after Day 42.
Secondary graft rejection is defined as the presence of less than 20% donor derived hematopoietic cells in peripheral blood or bone marrow that occurs after prior evidence of 20% or greater donor cells.
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1 year
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Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD)
Time Frame: 100 days
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Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash
Liver stage (based on bilirubin level)*: 0: <2 mg/dL
GI stage*: 0: No diarrhea or diarrhea <500 mL/day
GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4 |
100 days
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Percentage of Participants With Chronic GVHD
Time Frame: 1 year post-transplant
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Chronic GVHD is defined per NIH 2005 Consensus Criteria.
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1 year post-transplant
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Number of Participants With Chronic GVHD by Severity
Time Frame: 1 year post-transplant
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Chronic GVHD severity is defined per NIH 2005 Consensus Criteria.
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1 year post-transplant
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Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES)
Time Frame: 1 year
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1 year
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Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL)
Time Frame: 100 days post-transplant
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HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87).
The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 100 post-transplant will be evaluated.
Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being.
Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
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100 days post-transplant
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Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Time Frame: 100 days post-transplant
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HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87).
The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 100 post-transplant will be evaluated.
Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being.
Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
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100 days post-transplant
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Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL)
Time Frame: 180 days post-transplant
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HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87).
The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 180 post-transplant will be evaluated.
Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being.
Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
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180 days post-transplant
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Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Time Frame: 180 days post-transplant
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HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87).
The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to day 180 post-transplant will be evaluated.
Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being.
Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
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180 days post-transplant
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Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL)
Time Frame: 1 year post-transplant
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HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87).
The changes in participant reported scores on these HRQL subscales from a pre-transplant baseline assessment to 1 year post-transplant will be evaluated.
Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being.
Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
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1 year post-transplant
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Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Time Frame: 1 year post-transplant
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HRQL will be assessed using the Self-Esteem, General Health Perception, and Change in Health subscales of the Child Health Questionnaire (CHQ Child Form 87).
The changes in parent proxy reported scores on these HRQL subscales from a pre-transplant baseline assessment to 1 year post-transplant will be evaluated.
Each subscale is scored is scored in the range 0-100, with higher scores indicating better health and well-being.
Therefore, a negative mean change in score denotes worsening HRQL score and positive mean change in score denotes an improved HRQL score over time.
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1 year post-transplant
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Collaborators and Investigators
Publications and helpful links
General Publications
- Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
- Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
- Shenoy S, Eapen M, Panepinto JA, Logan BR, Wu J, Abraham A, Brochstein J, Chaudhury S, Godder K, Haight AE, Kasow KA, Leung K, Andreansky M, Bhatia M, Dalal J, Haines H, Jaroscak J, Lazarus HM, Levine JE, Krishnamurti L, Margolis D, Megason GC, Yu LC, Pulsipher MA, Gersten I, DiFronzo N, Horowitz MM, Walters MC, Kamani N. A trial of unrelated donor marrow transplantation for children with severe sickle cell disease. Blood. 2016 Nov 24;128(21):2561-2567. doi: 10.1182/blood-2016-05-715870. Epub 2016 Sep 13.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BMTCTN0601
- U01HL069294 (U.S. NIH Grant/Contract)
- 5U24CA076518 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Informed Consent Form (ICF)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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