Brief Summary
This is a clinical trial that will compare survival and sickle related outcomes in adolescents and young adults with severe sickle cell disease after bone marrow transplantation and standard of care. The primary outcome is 2-year overall survival.
Brief Title
Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503)
Detailed Description
This is a prospective phase II multi-center trial of hematopoietic stem cell transplantation or standard of care based on availability of HLA-matched related or unrelated donor after confirmation of clinical eligibility. In order to minimize bias assignment to either treatment arm, clinical eligibility to both treatment arms are similar and donor availability is not known at referral. HLA typing and donor search is initiated upon confirmation of clinical eligibility for the study. Additionally, all analyses of primary and secondary endpoints will follow the Intent-to-Treat principle to address potential bias introduced by participants with donors not proceeding to transplantation or those without a matched donor receiving transplantation with less well-matched donors.
The primary outcome is 2-year overall survival. Our hypothesis is that patients who receive bone marrow transplantation will experience early deaths but that this will plateau by 2 years after transplantation. Patients who receive standard of care will not experience early death but will succumb to their disease at a rate much higher than the general population. Therefore, the goal of the study is to establish that the difference in the proportion of patients surviving is not significantly more than 15% lower in the donor arm at 2-years after assignment to treatment arm.
Secondary endpoints will compare changes in sickle cell disease related events (pulmonary hypertension, cerebrovascular events, renal function, avascular necrosis, leg ulcer) and functional outcomes \[6-minute walk distance (6MWD), health-related quality of life, cardiac function, pulmonary function, and mean pain intensity as assessed by a multidimensional electronic pain diary\] from baseline to 2-years after assignment to treatment arms.
Additionally for patients assigned to the donor arm and expected to undergo transplantation, hematopoietic recovery, graft rejection, acute and chronic graft-versus-host disease, other significant transplant-related complications and disease-free survival will be reported.
The primary outcome is 2-year overall survival. Our hypothesis is that patients who receive bone marrow transplantation will experience early deaths but that this will plateau by 2 years after transplantation. Patients who receive standard of care will not experience early death but will succumb to their disease at a rate much higher than the general population. Therefore, the goal of the study is to establish that the difference in the proportion of patients surviving is not significantly more than 15% lower in the donor arm at 2-years after assignment to treatment arm.
Secondary endpoints will compare changes in sickle cell disease related events (pulmonary hypertension, cerebrovascular events, renal function, avascular necrosis, leg ulcer) and functional outcomes \[6-minute walk distance (6MWD), health-related quality of life, cardiac function, pulmonary function, and mean pain intensity as assessed by a multidimensional electronic pain diary\] from baseline to 2-years after assignment to treatment arms.
Additionally for patients assigned to the donor arm and expected to undergo transplantation, hematopoietic recovery, graft rejection, acute and chronic graft-versus-host disease, other significant transplant-related complications and disease-free survival will be reported.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 15 and \< 41 years
2. Severe sickle cell disease \[Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb Sβ) genotype\] with at least 1 of the following manifestations (a-e):
1. Clinically significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours;
2. 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);
3. An average of three or more pain crises per year in the 2-year period preceding enrollment (required intravenous pain management in the outpatient or inpatient hospital setting). Clinical documentation of pain management in the inpatient or outpatient setting is required.
4. Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
6. Ongoing high impact chronic pain on a majority of days per month for ≥ 6 months as defined as ONE or more of the following: Chronic pain without contributory SCD complications, OR Mixed pain type in which chronic pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to any sites associated with Contributory SCD complications (e.g. leg ulcers and/or avascular necrosis).
i. High impact chronic pain is identified as those reporting "severe interference" with life activities OR "usually or always" experiencing a limitation of their life or work activities including household chores. (See guidelines for identifying HICP in the BMT CTN 1503 Manual of Procedures) ii. Contributory SCD complications are defined as clinical signs (e.g. presence of leg ulcers) or clinical assessments (e.g. imaging confirmation of splenic infarct or avascular necrosis). Chronic pain attributed solely to contributory SCD complications is excluded.
3. Adequate physical function as measured by all of the following:
1. Karnofsky/Lansky performance score ≥ 60
2. Cardiac function: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
3. Pulmonary function:
a. Pulse oximetry with a baseline O2 saturation of ≥ 85% b. Diffusing capacity of the lung for carbon monoxide (DLCO) \> 40% (corrected for hemoglobin) d. Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and 24 hour urine creatinine clearance \>70 mL/min; or GFR \> 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR).
e. Hepatic function:
1. Serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory. Participants are not excluded if the serum conjugated (direct) bilirubin is \>2x the upper limit of normal for age as per local laboratory and: There is evidence of a hyperhemolytic reaction after a recent RBC transfusion, OR there is evidence of moderate direct hyperbilirubinemia defined as direct serum bilirubin \< 5 times ULN and not caused by underlying hepatic diseasePatients
2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 times upper limit of normal as per local laboratory.
Additional inclusion required for donor arm participants to proceed with transplant
1. Liver MRI (≤ 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ≥7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (≤ 90 days prior to initiation of transplant conditioning).
2. Lack of clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) by Cerebral MRI/MRA within 30 days prior to initiating transplant conditioning. Subjects with clinical or radiologic evidence of a recent neurologic event will be deferred for ≥ 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation
3. Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications is to be documented in the medical record corresponding with the consent conference.
Exclusion Criteria:
1. HLA typing with a donor search prior to referral (consultation with HCT physician).
1. If a subject has had HLA typing and a related donor search that did not identify a suitably matched relative (i.e., sibling) at any time, and also did not have an unrelated donor search, the patient will be considered eligible.
2. If a subject has had HLA typing and a related donor search that did not identify a suitably matched relative (i.e., sibling) at any time and had an unrelated donor search that did not identify a suitably matched unrelated donor ≥ 1 year prior to enrollment, the patient will be considered eligible.
3. If a subject has had HLA typing with no related donor search and had an unrelated donor search that did not identify a suitably matched unrelated donor ≥ 1 year prior to enrollment, the patient will be considered eligible.
4. Subjects with a known HLA-identical sibling or HLA-matched unrelated donor are excluded
2. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
3. Seropositivity for HIV.
4. Previous HCT or solid organ transplant.
5. Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
6. A history of substance abuse as defined by version IV of the Diagnostic \& Statistical Manual of Mental Disorders (DSM IV).
7. Demonstrated lack of compliance with prior medical care as determined by referring physician.
8. Pregnant or breast feeding females.
9. Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy.
1. Age ≥ 15 and \< 41 years
2. Severe sickle cell disease \[Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb Sβ) genotype\] with at least 1 of the following manifestations (a-e):
1. Clinically significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours;
2. 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);
3. An average of three or more pain crises per year in the 2-year period preceding enrollment (required intravenous pain management in the outpatient or inpatient hospital setting). Clinical documentation of pain management in the inpatient or outpatient setting is required.
4. Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
6. Ongoing high impact chronic pain on a majority of days per month for ≥ 6 months as defined as ONE or more of the following: Chronic pain without contributory SCD complications, OR Mixed pain type in which chronic pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to any sites associated with Contributory SCD complications (e.g. leg ulcers and/or avascular necrosis).
i. High impact chronic pain is identified as those reporting "severe interference" with life activities OR "usually or always" experiencing a limitation of their life or work activities including household chores. (See guidelines for identifying HICP in the BMT CTN 1503 Manual of Procedures) ii. Contributory SCD complications are defined as clinical signs (e.g. presence of leg ulcers) or clinical assessments (e.g. imaging confirmation of splenic infarct or avascular necrosis). Chronic pain attributed solely to contributory SCD complications is excluded.
3. Adequate physical function as measured by all of the following:
1. Karnofsky/Lansky performance score ≥ 60
2. Cardiac function: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
3. Pulmonary function:
a. Pulse oximetry with a baseline O2 saturation of ≥ 85% b. Diffusing capacity of the lung for carbon monoxide (DLCO) \> 40% (corrected for hemoglobin) d. Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and 24 hour urine creatinine clearance \>70 mL/min; or GFR \> 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR).
e. Hepatic function:
1. Serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory. Participants are not excluded if the serum conjugated (direct) bilirubin is \>2x the upper limit of normal for age as per local laboratory and: There is evidence of a hyperhemolytic reaction after a recent RBC transfusion, OR there is evidence of moderate direct hyperbilirubinemia defined as direct serum bilirubin \< 5 times ULN and not caused by underlying hepatic diseasePatients
2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 times upper limit of normal as per local laboratory.
Additional inclusion required for donor arm participants to proceed with transplant
1. Liver MRI (≤ 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ≥7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (≤ 90 days prior to initiation of transplant conditioning).
2. Lack of clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) by Cerebral MRI/MRA within 30 days prior to initiating transplant conditioning. Subjects with clinical or radiologic evidence of a recent neurologic event will be deferred for ≥ 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation
3. Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications is to be documented in the medical record corresponding with the consent conference.
Exclusion Criteria:
1. HLA typing with a donor search prior to referral (consultation with HCT physician).
1. If a subject has had HLA typing and a related donor search that did not identify a suitably matched relative (i.e., sibling) at any time, and also did not have an unrelated donor search, the patient will be considered eligible.
2. If a subject has had HLA typing and a related donor search that did not identify a suitably matched relative (i.e., sibling) at any time and had an unrelated donor search that did not identify a suitably matched unrelated donor ≥ 1 year prior to enrollment, the patient will be considered eligible.
3. If a subject has had HLA typing with no related donor search and had an unrelated donor search that did not identify a suitably matched unrelated donor ≥ 1 year prior to enrollment, the patient will be considered eligible.
4. Subjects with a known HLA-identical sibling or HLA-matched unrelated donor are excluded
2. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
3. Seropositivity for HIV.
4. Previous HCT or solid organ transplant.
5. Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
6. A history of substance abuse as defined by version IV of the Diagnostic \& Statistical Manual of Mental Disorders (DSM IV).
7. Demonstrated lack of compliance with prior medical care as determined by referring physician.
8. Pregnant or breast feeding females.
9. Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy.
Inclusion Criteria
Inclusion Criteria:
1. Age ≥ 15 and \< 41 years
2. Severe sickle cell disease \[Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb Sβ) genotype\] with at least 1 of the following manifestations (a-e):
1. Clinically significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours;
2. 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);
3. An average of three or more pain crises per year in the 2-year period preceding enrollment (required intravenous pain management in the outpatient or inpatient hospital setting). Clinical documentation of pain management in the inpatient or outpatient setting is required.
4. Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
6. Ongoing high impact chronic pain on a majority of days per month for ≥ 6 months as defined as ONE or more of the following: Chronic pain without contributory SCD complications, OR Mixed pain type in which chronic pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to any sites associated with Contributory SCD complications (e.g. leg ulcers and/or avascular necrosis).
i. High impact chronic pain is identified as those reporting "severe interference" with life activities OR "usually or always" experiencing a limitation of their life or work activities including household chores. (See guidelines for identifying HICP in the BMT CTN 1503 Manual of Procedures) ii. Contributory SCD complications are defined as clinical signs (e.g. presence of leg ulcers) or clinical assessments (e.g. imaging confirmation of splenic infarct or avascular necrosis). Chronic pain attributed solely to contributory SCD complications is excluded.
3. Adequate physical function as measured by all of the following:
1. Karnofsky/Lansky performance score ≥ 60
2. Cardiac function: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
3. Pulmonary function:
a. Pulse oximetry with a baseline O2 saturation of ≥ 85% b. Diffusing capacity of the lung for carbon monoxide (DLCO) \> 40% (corrected for hemoglobin) d. Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and 24 hour urine creatinine clearance \>70 mL/min; or GFR \> 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR).
e. Hepatic function:
1. Serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory. Participants are not excluded if the serum conjugated (direct) bilirubin is \>2x the upper limit of normal for age as per local laboratory and: There is evidence of a hyperhemolytic reaction after a recent RBC transfusion, OR there is evidence of moderate direct hyperbilirubinemia defined as direct serum bilirubin \< 5 times ULN and not caused by underlying hepatic diseasePatients
2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 times upper limit of normal as per local laboratory.
Additional inclusion required for donor arm participants to proceed with transplant
1. Liver MRI (≤ 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ≥7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (≤ 90 days prior to initiation of transplant conditioning).
2. Lack of clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) by Cerebral MRI/MRA within 30 days prior to initiating transplant conditioning. Subjects with clinical or radiologic evidence of a recent neurologic event will be deferred for ≥ 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation
3. Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications is to be documented in the medical record corresponding with the consent conference.
1. Age ≥ 15 and \< 41 years
2. Severe sickle cell disease \[Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb Sβ) genotype\] with at least 1 of the following manifestations (a-e):
1. Clinically significant neurologic event (stroke) or any neurological deficit lasting \> 24 hours;
2. 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);
3. An average of three or more pain crises per year in the 2-year period preceding enrollment (required intravenous pain management in the outpatient or inpatient hospital setting). Clinical documentation of pain management in the inpatient or outpatient setting is required.
4. Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
6. Ongoing high impact chronic pain on a majority of days per month for ≥ 6 months as defined as ONE or more of the following: Chronic pain without contributory SCD complications, OR Mixed pain type in which chronic pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to any sites associated with Contributory SCD complications (e.g. leg ulcers and/or avascular necrosis).
i. High impact chronic pain is identified as those reporting "severe interference" with life activities OR "usually or always" experiencing a limitation of their life or work activities including household chores. (See guidelines for identifying HICP in the BMT CTN 1503 Manual of Procedures) ii. Contributory SCD complications are defined as clinical signs (e.g. presence of leg ulcers) or clinical assessments (e.g. imaging confirmation of splenic infarct or avascular necrosis). Chronic pain attributed solely to contributory SCD complications is excluded.
3. Adequate physical function as measured by all of the following:
1. Karnofsky/Lansky performance score ≥ 60
2. Cardiac function: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
3. Pulmonary function:
a. Pulse oximetry with a baseline O2 saturation of ≥ 85% b. Diffusing capacity of the lung for carbon monoxide (DLCO) \> 40% (corrected for hemoglobin) d. Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and 24 hour urine creatinine clearance \>70 mL/min; or GFR \> 70 mL/min/1.73 m2 by radionuclide Glomerular Filtration Rate (GFR).
e. Hepatic function:
1. Serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory. Participants are not excluded if the serum conjugated (direct) bilirubin is \>2x the upper limit of normal for age as per local laboratory and: There is evidence of a hyperhemolytic reaction after a recent RBC transfusion, OR there is evidence of moderate direct hyperbilirubinemia defined as direct serum bilirubin \< 5 times ULN and not caused by underlying hepatic diseasePatients
2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5 times upper limit of normal as per local laboratory.
Additional inclusion required for donor arm participants to proceed with transplant
1. Liver MRI (≤ 90 days prior to initiation of transplant conditioning) to document hepatic iron content is required for participants who are currently receiving ≥8 packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood cell transfusions (cumulative). Participants who have hepatic iron content ≥7 mg Fe/ g liver dry weight by liver MRI must have a liver biopsy and histological examination/documentation of the absence of cirrhosis, bridging fibrosis and active hepatitis (≤ 90 days prior to initiation of transplant conditioning).
2. Lack of clinical or radiologic evidence of a recent neurologic event (such as stroke or transient ischemic attack) by Cerebral MRI/MRA within 30 days prior to initiating transplant conditioning. Subjects with clinical or radiologic evidence of a recent neurologic event will be deferred for ≥ 6 months with repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to proceeding to transplantation
3. Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications is to be documented in the medical record corresponding with the consent conference.
Gender
All
Gender Based
false
Keywords
Sickle Cell Disease
Young Adults
Phase II Trial
Hematopoietic Cell Transplantation (HCT)
Human Leukocyte Antigen (HLA)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
40 Years
Minimum Age
15 Years
NCT Id
NCT02766465
Org Class
Other
Org Full Name
Medical College of Wisconsin
Org Study Id
BMT CTN 1503
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults With Severe Sickle Cell Disease (BMT CTN 1503)
Primary Outcomes
Outcome Description
Due to incomplete accrual, there was not adequate statistical power to analyze the primary endpoint as specified. Instead, point estimates for the observed proportion of patients surviving at two years post-biologic assignment in each arm were generated descriptively, with 95% CI, using the Kaplan Meier methodology. The event of interest was death from any cause.
Outcome Measure
Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment
Outcome Time Frame
2 Years
Secondary Ids
Secondary Id
1U01HL128568-01
Secondary Outcomes
Outcome Description
Examination of the occurrence of the SCD-related events was performed. Participants can have multiple events. The following sickle cell disease related events of special interest (SCD-EOSI) are expected events for all participants, regardless of biologic assignment:
* pulmonary hypertension
* significant cerebrovascular events, including: stroke; transient ischemic attack; seizure
* renal function compromise, including: proteinuria; increased creatinine grades ≥2 per CTCAE version 4.0
* avascular necrosis of the hip or shoulder
* leg ulcers
* acute chest syndrome (ACS) requiring hospitalization
* vaso-occlusive pain crisis (VOC) requiring hospitalization or administration of parenteral opioid drugs in an outpatient setting. Self-reported events without clinical documentation should not be included.
* pulmonary hypertension
* significant cerebrovascular events, including: stroke; transient ischemic attack; seizure
* renal function compromise, including: proteinuria; increased creatinine grades ≥2 per CTCAE version 4.0
* avascular necrosis of the hip or shoulder
* leg ulcers
* acute chest syndrome (ACS) requiring hospitalization
* vaso-occlusive pain crisis (VOC) requiring hospitalization or administration of parenteral opioid drugs in an outpatient setting. Self-reported events without clinical documentation should not be included.
Outcome Time Frame
2 Years
Outcome Measure
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest
Outcome Description
The 6-minute walk distance (6MWD) test is a test to measure how far you can walk in 6 minutes. It is used in this study to assess exercise capacity. The number of meters that a participant could walk in 6 minutes was selected as a direct measurement of physical function.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in 6-minute Walk Distance (6MWD) Assessment From Baseline
Outcome Description
Transcuspid regurgitant jet velocity (TRJV) is a measure of how fast blood is pumped through one of the heart valves on the right side of the heart, measured using an ultrasound of the heart (echocardiogram). Higher values can indicate pulmonary hypertension and more severe sickle cell disease. Increasing TRJV over time indicates worsening disease.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline
Outcome Description
Albuminuria is the ratio of albumin (a protein) in the urine to creatinine in the urine. This may be assessed based on a 24-hour urine sample or a spot urine sample. Albumin in the urine may indicate kidney disease. Increases in albuminuria over time indicate increasing renal (kidney) disease.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Albuminuria Assessment From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Physical Function asks about degree of difficulty in performing activities of daily living such as housework, errands, and going up and down stairs. 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 better physical function.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Anxiety asks about the frequency of feelings of fear, worry, and anxiety. 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 more anxiety.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Depression asks about the frequency of feelings of worthlessness, failure, unhappiness and depression. 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 more depression.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Fatigue asks about the extent to which fatigue interferes with physical functioning and completing tasks. 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 more fatigue.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Sleep Disturbance asks about the quality of sleep and the frequency with which sleep was restless or difficult to achieve. 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 more sleep disturbance.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Participation in Social Roles asks about the frequency of limitations of social activities with friends and family. 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 more satisfaction with participation in social roles.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Pain Interference asks about the frequency with which pain interferes with household chores, social activities and enjoyment of life. 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 more pain interference in daily life.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. Pain Intensity is scored from 0 to 10 reflecting the level of pain over the previous 7 days. A score of 0 reflects no pain; a score of 10 reflects the maximum intensity of pain.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. The 28-Day Pain Diary Average Pain Intensity assesses pain on a score of 0 to 10 twice each day for 28 days. A score of 0 reflects no pain, and a score of 10 reflects maximum intensity of pain. The scores on a given day are averaged (if only one score is obtained on a given day, that score is taken as the measure), and then daily scores are averaged over the number of days on which a score is available.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline
Outcome Description
Health-Related Quality of Life (HRQoL) assessed using the NIH's PROMIS 57 instrument. The ASCQ-Me Stiffness Scale asks about the frequency and severity of joint stiffness. 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 more stiffness.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in Forced Expiratory Volume 1 second (FEV1). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in forced vital capacity (FVC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in ratio of FEV1 to FVC (FEV1/FVC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in vital capacity (VC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Vital Capacity (VC) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in total lung capacity (TLC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in residual volume (RV). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Residual Volume (RV) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in expiratory reserve volume (ERV). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in inspiratory capacity (IC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in functional residual capacity (FRC). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in diffusing capacity for carbon monoxide (DLCO). The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline
Outcome Description
Pulmonary function is assessed by the change from baseline in oxygen saturation. The complete pulmonary function test will include forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), ratio of FEV1 to FVC (FEV1/FVC), vital capacity (VC), total lung capacity (TLC), residual volume (RV), expiratory reserve volume (ERV), inspiratory capacity (IC), functional residual capacity (FRC), diffusing capacity for carbon monoxide (DLCO), and oxygen saturation.
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Change in Pulmonary Function of Oxygen Saturation From Baseline
Outcome Description
All Grade 2 and 3 infections were reported according to the BMT CTN Technical Manual of Procedures (MOP) after biological assignment. The frequency of Grade 2-3 infections are tabulated by biological assignment at the event level.
Outcome Time Frame
2 years
Outcome Measure
Frequencies of Infections
Outcome Description
The time interval from day 0 of transplant until grade II-IV aGVHD will be described for each treatment arm using the the cumulative incidence estimator developed by Gray, with death prior to aGVHD treated as a competing risk. Estimates and 95% CIs of the cumulative incidence of grade II-IV aGVHD will be provided at Day 180 after day 0 of transplant and compared between matched related and matched unrelated donors using the Gray test.
Acute GVHD was graded according to the BMT CTN Technical Manual of Operating Procedures (MOP). Higher aGVHD grade indicate worse outcomes. Grade I is defined as Skin stage 1-2 and stage 0 for both GI and liver. Grade II is stage 3 skin, stage 1 GI, or stage 1 liver. Grade III is stage 2-3 GI or stage 2-3 liver. Grade IV is stage 4 skin or stage 4 liver.
Acute GVHD was graded according to the BMT CTN Technical Manual of Operating Procedures (MOP). Higher aGVHD grade indicate worse outcomes. Grade I is defined as Skin stage 1-2 and stage 0 for both GI and liver. Grade II is stage 3 skin, stage 1 GI, or stage 1 liver. Grade III is stage 2-3 GI or stage 2-3 liver. Grade IV is stage 4 skin or stage 4 liver.
Outcome Time Frame
180 days after biological assignment
Outcome Measure
Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment
Outcome Description
Chronic GVHD was collected according to the recommendations of the NIH Consensus Conference. Eight organs will be scored on a 0-3 scale to reflect degree of chronic GVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of chronic GVHD was also recorded. Percentage of Participants with chronic GVHD (cGVHD) at Day 600 was estimated with 95% confidence intervals for each donor type group using the cumulative incidence estimate, treating death prior to cGVHD as a competing event.
Outcome Time Frame
Day 600 after biological assignment
Outcome Measure
Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment
Outcome Description
Primary graft failure defined as never achieving ANC ≥ 500/µL or never achieving ≥ 5% donor whole blood or myeloid chimerism (myeloid is preferable) assessed by bone marrow or peripheral blood chimerism assays by day +42 post-transplant. Second infusion of hematopoietic cells is also considered indicative of primary graft failure by day +42 post-transplant. Secondary graft failure is defined as \< 5% donor whole blood or myeloid chimerism (myeloid is preferable) 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. Second infusion of hematopoietic cells is also considered indicative of secondary graft failure.
Outcome Time Frame
2 years
Outcome Measure
Number of Participants With Primary and Secondary Graft Failure
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
40
Minimum Age Number (converted to Years and rounded down)
15
Investigators
Investigator Type
Principal Investigator
Investigator Name
Caterina Minniti
Investigator Email
caterina.minniti@einsteinmed.org
Investigator Phone