Sickle Cell DiseasePhase 2SCURTNCT00745420
Evaluating the Safety and Effectiveness of Bone Marrow Transplants in Children With Sickle Cell Disease (BMT CTN 0601)
A Phase 2 study testing Hematopoietic Stem Cell Transplantation in people with Sickle Cell Disease, run by Medical College of Wisconsin at 19 sites in United States.
Trial summary
Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause organ damage, stroke, and intense pain episodes. A blood stem cell transplant is a treatment option for someone with a severe form of the disease. Read more about this study
- Who is it for?
- Ages 3 to 19 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Hematopoietic Stem Cell Transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 19 sitesUnited States
- Study dates
- Aug 2008to Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 3 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48105
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60614
University Hospitals of Cleveland
Cleveland, Ohio, 44106
Baylor College of Medicine/The Methodist Hospital
Houston, Texas, 77030
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Children's Mercy Hospital and Clinics
Kansas City, Missouri, 64108
University of Miami
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53211
Cohen Children's Hospital
New Hyde Park, New York, 11040
Children's Hospital of New Orleans/LSUMC CCOP
New Orleans, Louisiana, 70118
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Virginia Commonwealth University
Richmond, Virginia, 23298
Washington University, St. Louis Children's Hospital
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children With Severe Sickle Cell Disease (BMT CTN #0601)
Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause organ damage, stroke, and intense pain episodes. A blood stem cell transplant is a treatment option for someone with a severe form of the disease. Prior to undergoing a transplant, people typically receive a conditioning regimen of high doses of chemotherapy and other medications to prepare the body to accept the transplant. A conditioning regimen that uses lower doses of chemotherapy and medications may be safer for transplant recipients. This study will evaluate 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 prior to the transplant.
Read the 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Hematopoietic Stem Cell Transplantation
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia
- 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.
Hematopoietic Stem Cell TransplantationBiological
Also called Bone Marrow Transplant
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.
- Alemtuzumab: Children weighing 10 kg or more will receive 10 mg, 15 mg, and 20 mg intravenously (IV) on Days -21, -20, and -19, respectively
- Fludarabine: 30 mg/m^2/day IV on Days -8 through -4
- Melphalan: 140 mg/m^2 IV on Day -3
- Rest on Days -2 and -1
- Transplant occurs on Day 0
- GVHD prophylaxis: Tacrolimus or cyclosporine beginning Day -3, methotrexate (7.5 mg/m2/day) Day 1, 3 and 6 and methylprednisolone/prednisone on Day +7 to +28 followed by a taper if there is no GVHD
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Bone Marrow Transplant with GVHD Prophylaxis Regimen Receives: Biological: Hematopoietic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Event-Free Survival (EFS)
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.
Measured: 2 years
Secondary outcomes (13)
Percentage of Participants With Overall Survival (OS)
OS is defined as the percentage of participants that have not died.
Measured: 2 years
Neutrophil and Platelet Recovery
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.
Measured: Up to 100 days
Graft Rejection
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.
Measured: 1 year
Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD)
Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:
Skin stage:
0: No rash
- Rash <25% of body surface area
- Rash on 25-50% of body surface area
- Rash on > 50% of body surface area
- Generalized erythroderma with bullous formation
Liver stage (based on bilirubin level)*:
0: <2 mg/dL
- 2-3 mg/dL
- 3.01-6 mg/dL
- 6.01-15.0 mg/dL
- >15 mg/dL
GI stage*:
0: No diarrhea or diarrhea <500 mL/day
- Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
- Diarrhea 1000-1499 mL/day
- Diarrhea >1500 mL/day
- Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.
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
Measured: 100 days
Percentage of Participants With Chronic GVHD
Chronic GVHD is defined per NIH 2005 Consensus Criteria.
Measured: 1 year post-transplant
Number of Participants With Chronic GVHD by Severity
Chronic GVHD severity is defined per NIH 2005 Consensus Criteria.
Measured: 1 year post-transplant
Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES)
Measured: 1 year
Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL)
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.
Measured: 100 days post-transplant
Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
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.
Measured: 100 days post-transplant
Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL)
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.
Measured: 180 days post-transplant
Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
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.
Measured: 180 days post-transplant
Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL)
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.
Measured: 1 year post-transplant
Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL)
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.
Measured: 1 year post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2008 (estimated)
- Study startAug 2008
- Primary completionJul 2015
- Study completionSep 2016
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 (5)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 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), Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Marrow Donor Program, Sickle Cell Disease Clinical Research Network
- Responsible party
- Sponsor
- Investigators
- Mary Horowitz, MD, Study director, Center for International Blood and Marrow Transplant Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00745420
- Sponsor's protocol ID
- BMTCTN0601
- Other IDs
- U01HL069294, 5U24CA076518
- Acronym
- SCURT
- Status last verified
- Dec 2022
- First submitted
- 29 Aug 2008
- Last updated
- 9 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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
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.
PubMed 16338616Przepiorka 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.
PubMed 7581076Shenoy 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.
PubMed 27625358Martens MJ, Logan BR. Statistical rules for safety monitoring in clinical trials. Clin Trials. 2024 Apr;21(2):152-161. doi: 10.1177/17407745231203391. Epub 2023 Oct 25.
PubMed 37877375Leonard 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
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children With Severe Sickle Cell Disease (BMT CTN #0601)
- ClinicalTrials.gov ID
- NCT00745420
- Acronym / sponsor ID
- SCURT / BMTCTN0601
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Sickle Cell Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Marrow Donor Program, Sickle Cell Disease Clinical Research Network
- Study start
- Aug 2008
- Primary completion
- Jul 2015 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 3 Sep 2008 (estimated)
- Results
- Posted 26 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease that can cause organ damage, stroke, and intense pain episodes. A blood stem cell transplant is a treatment option for someone with a severe form of the disease. Prior to undergoing a transplant, people typically receive a conditioning regimen of high doses of chemotherapy and other medications to prepare the body to accept the transplant. A conditioning regimen that uses lower doses of chemotherapy and medications may be safer for transplant recipients. This study will evaluate 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 prior to the transplant.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Biological: Hematopoietic Stem Cell TransplantationBone Marrow Transplant with GVHD Prophylaxis Regimen |
Who may qualify
- Ages
- 3 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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:
- 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.
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| Hematopoietic Stem Cell TransplantationAlso: Bone Marrow TransplantThe 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. * Alemtuzumab: Children weighing 10 kg or more will receive 10 mg, 15 mg, and 20 mg intravenously (IV) on Days -21, -20, and -19, respectively * Fludarabine: 30 mg/m^2/day IV on Days -8 through -4 * Melphalan: 140 mg/m^2 IV on Day -3 * Rest on Days -2 and -1 * Transplant occurs on Day 0 * GVHD prophylaxis: Tacrolimus or cyclosporine beginning Day -3, methotrexate (7.5 mg/m2/day) Day 1, 3 and 6 and methylprednisolone/prednisone on Day +7 to +28 followed by a taper if there is no GVHD | Biological | Hematopoietic Stem Cell Transplantation |
Primary outcome
Percentage of Participants With Event-Free Survival (EFS)
Time frame: 2 years
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.
13 secondary outcomes
Percentage of Participants With Overall Survival (OS)
Time frame: 2 years
Neutrophil and Platelet Recovery
Time frame: Up to 100 days
Graft Rejection
Time frame: 1 year
Percentage of Participants With Acute Graft-vs-Host-Disease (GVHD)
Time frame: 100 days
Percentage of Participants With Chronic GVHD
Time frame: 1 year post-transplant
Number of Participants With Chronic GVHD by Severity
Time frame: 1 year post-transplant
Percentage of Participants With Posterior Reversible Encephalopathy Syndrome (PRES)
Time frame: 1 year
Change From Baseline to Day 100 in Participant Reported Health-Related Quality of Life (HRQL)
Time frame: 100 days post-transplant
Change From Baseline to Day 100 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Time frame: 100 days post-transplant
Change From Baseline to Day 180 in Participant Reported Health-Related Quality of Life (HRQL)
Time frame: 180 days post-transplant
Change From Baseline to Day 180 in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Time frame: 180 days post-transplant
Change From Baseline to 1 Year in Participant Reported Health-Related Quality of Life (HRQL)
Time frame: 1 year post-transplant
Change From Baseline to 1 Year in Parent Proxy Reported Health-Related Quality of Life (HRQL)
Time frame: 1 year post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16338616Filipovich 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.
- Background: PubMed 7581076Przepiorka 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.
- Results publication: PubMed 27625358Shenoy 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.
- Derived from this study: PubMed 37877375Martens MJ, Logan BR. Statistical rules for safety monitoring in clinical trials. Clin Trials. 2024 Apr;21(2):152-161. doi: 10.1177/17407745231203391. Epub 2023 Oct 25.
- Derived from this study: PubMed 36240296Leonard 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.
- Individual participant dataSharing planned: 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).
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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. This study is not recruiting at the moment.
Mary Horowitz, MD study director
Center for International Blood and Marrow Transplant Research
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hematopoietic Stem Cell Transplantation in people with Sickle Cell Disease, run by Medical College of Wisconsin at 19 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 9 inclusion and 7 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: finished, as of the sponsor's last update on 9 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 26 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Event-Free Survival (EFS) (time frame: 2 years). 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 NCT00745420, which also lists 5 linked publications.
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 9 Dec 2022.