Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, Young Adults, Phase II Trial, Hematopoietic Cell Transplantation (HCT), Human Leukocyte Antigen (HLA)
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.
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.
Interventions
DRUGBusulfan
A: Busulfan dose will be 3.2 mg/kg administered as a single daily dose IV on days -8 through -5 with dosing adjusted using targeted pharmacokinetics.
DRUGFludarabine
A: Fludarabine dose will be 35 mg/m\^2/day administered IV on days -7 through -3 (total fludarabine dose is 175 mg/m\^2). C: Fludarabine 30mg/m2 IV dose will be given on Days -8, -7, -6, -5, -4
DRUGr-ATG
A: r-ATG will be administered IV on day -6 at 0.5mg/kg, on day -5 at 1 mg/kg and on days -4, -3 and -2 at 1.5mg/kg (total r-ATG dose is 6 mg/kg).
PROCEDUREHematopoietic Cell Transplant
A,B,C: Day 0 is the day of transplantation.
DRUGTacrolimus
A: Tacrolimus commences on day -3 and extends through day +180 after transplantation with doses adjusted to maintain appropriate levels according to institutional guidelines. C: Tacrolimus at therapeutic doses through Day 180, then taper per institutional guidelines
DRUGMethotrexate
A: Methotrexate will be administered intravenously on day+1 at 15mg/m\^2, day+3 at 10mg/m\^2, day+6 at 10mg/m\^2, and day+11 at 10mg/m\^2. C: Methotrexate IV 7.5 mg/m2 dose will be given on Days +1, 3, +6 following transplant
PROCEDUREStandard of Care
Continue to receive standard of care treatment per patient's SCD physician.
DRUGAlemtuzumab
B: Alemtuzumab 0.03 mg/kg IV dose will be given on Day -7, Alemtuzumab 0.1 mg/kg IV dose will be given on Day -6, Alemtuzumab 0.3 mg/kg IV dose will be given on Day -5,-4,-3 C: Alemtuzumab test dose 3 mg IV once 24 hours prior to 1st dose of Alemtuzumab Alemtuzumab 10 mg IV, 15 mg IV, 20 mg IV given on Days -22 through Day -18. Alemtuzumab doses may be administered between Days -22 and -18 but are required to be on three consecutive days.
DRUGTotal Body Irradiation (TBI)
Total Body Irradiation 300 cGY on Day -2
DRUGSirolimus
Sirolimus at therapeutic doses through day 180, then taper per institutional guidelines if donor CD3+ \>50%
DRUGMelphalan
C: Melphalan 140 mg/m2 IV dose will be given on Day -3
DRUGG-CSF
G-CSF 5 μg/kg/day continue until neutrophil engraftment.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
Dana-Farber Cancer Institute
National Marrow Donor Program
Emory University
Medical College of Wisconsin
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients are enrolled without a known donor. All patients have 180 days from confirmation of eligibility to confirm a donor. Patients with a donor will be assigned to the Donor Arm and receive HCT; patients without a donor will be assigned to the no donor arm and continue receiving standard of care for their SCD.
Eligibility
Sex/Gender
ALL
Age
15 Years to 40 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment | 2 Years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | 2 Years | 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. |
| Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline | Baseline, 2 years | 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. |
| Change in Albuminuria Assessment From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline | Baseline, 2 years | 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. |
| Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline | Baseline, 2 years | 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. |
| Change in 6-minute Walk Distance (6MWD) Assessment From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Vital Capacity (VC) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Residual Volume (RV) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline | Baseline, 2 years | 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. |
| Change in Pulmonary Function of Oxygen Saturation From Baseline | Baseline, 2 years | 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. |
| Frequencies of Infections | 2 years | 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. |
| Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment | 180 days after biological assignment | 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. |
| Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment | Day 600 after biological assignment | 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. |
| Number of Participants With Primary and Secondary Graft Failure | 2 years | 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. |
| Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline | Baseline, 2 years | 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. |
Countries
United States
Participant flow
Recruitment details
BMT CTN 1503's enrollment was between March 2017 and August 2021. The study opened to accrual on March 16, 2017 with activated 37 centers. The study closed to accrual on August 31, 2021 and study completed on May 2, 2023. A total of 138 eligible participants were enrolled to Segment 0 from 31 centers.
Pre-assignment details
Among 138 enrolled patients, 123 were biologically assigned and enrolled in Segment A. Of the 15 who were not biologically assigned, 2 died prior to assignment due to SCD complications, 10 withdrew consent, 2 lost to follow-up, and 1 was removed per physician decision. Of the 123 biologically assigned patients, 28 patients across 13 institutions were assigned to the Donor Arm and 95 patients across 26 institutions were assigned to the No Donor Arm. In the donor arm 24 patients were transplanted.
Participants by arm
| Arm | Count |
|---|---|
| Donor Arm Donor Arm patients will undergo hematopoietic cell transplant. Patients with a matched unrelated donor will receive a bone marrow transplant (unless PBSC graft is pre-approved per section 2.5.1 using a preparative regimen with Busulfan, Fludarabine and rabbit ATG. Patients with an HLA-identical sibling donor can receive a transplant using one of three regimens:
A. Busulfan, Fludarabine, and rabbit ATG using a bone marrow graft (preferred regimen) B. Alemtuzumab/TBI 300 cGy using a peripheral blood graft C. Alemtuzumab, fludarabine, melphalan using a bone marrow graft | 28 |
| No-Donor Arm No-donor arm patients will continue with standard of care per their SCD physician.
Standard of Care: Continue to receive standard of care treatment per patient's SCD physician. | 85 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 10 |
Baseline characteristics
| Characteristic | No-Donor Arm | Total | Donor Arm |
|---|---|---|---|
| Age, Continuous | 25.9 years | 26.2 years | 29.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 12 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 99 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized African American | 41 Participants | 53 Participants | 12 Participants |
| Race/Ethnicity, Customized African Black (both parents African) | 7 Participants | 7 Participants | 0 Participants |
| Race/Ethnicity, Customized Black (NOS) | 22 Participants | 35 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 73 Participants | 99 Participants | 26 Participants |
| Race/Ethnicity, Customized Caribbean Black | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Middle Eastern | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not answered | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Puerto Rican | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Saudi Arabian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized South or Central American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized South or Central American Black | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 6 Participants | 1 Participants |
| Race/Ethnicity, Customized White (NOS) | 3 Participants | 4 Participants | 1 Participants |
| Severity of SCD Criteria Acute Chest Syndrome (ACS) | 14 Participants | 15 Participants | 1 Participants |
| Severity of SCD Criteria High Impact Chronic Pain | 19 Participants | 29 Participants | 10 Participants |
| Severity of SCD Criteria Neurologic | 7 Participants | 14 Participants | 7 Participants |
| Severity of SCD Criteria Pain Crises | 62 Participants | 79 Participants | 17 Participants |
| Severity of SCD Criteria Red Blood Cell (RBC) Transfusion | 13 Participants | 20 Participants | 7 Participants |
| Severity of SCD Criteria Tricuspid valve Regurgitant Jet Velocity (TRJV) | 9 Participants | 10 Participants | 1 Participants |
| Sex: Female, Male Female | 39 Participants | 54 Participants | 15 Participants |
| Sex: Female, Male Male | 46 Participants | 59 Participants | 13 Participants |
| Sickle Cell Disease Type HbS beta thalassemia | 9 Participants | 11 Participants | 2 Participants |
| Sickle Cell Disease Type HbSC | 4 Participants | 5 Participants | 1 Participants |
| Sickle Cell Disease Type HbS-OArab | 1 Participants | 1 Participants | 0 Participants |
| Sickle Cell Disease Type HbSS | 67 Participants | 88 Participants | 21 Participants |
| Sickle Cell Disease Type Unknown | 4 Participants | 8 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 28 | 5 / 85 |
| other Total, other adverse events | 14 / 28 | 65 / 85 |
| serious Total, serious adverse events | 0 / 28 | 0 / 85 |
Outcome results
Primary
Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment
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.
Time frame: 2 Years
Population: Using the intent-to-treat principle, participants remained in their assigned treatment arm regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Donor Arm | Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment | 89 percentage of participants |
| No-Donor Arm | Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment | 94 percentage of participants |
Secondary
Change in 6-minute Walk Distance (6MWD) Assessment From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in 6-minute Walk Distance (6MWD) Assessment From Baseline | -71 meter |
| No-Donor Arm | Change in 6-minute Walk Distance (6MWD) Assessment From Baseline | -26 meter |
Comparison: This is the result comparing 6MWD from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.869Wilcoxon (Mann-Whitney)
Secondary
Change in Albuminuria Assessment From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| No-Donor Arm | Change in Albuminuria Assessment From Baseline | 0 mg of albumin per gram of creatine |
Secondary
Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline | -4 percentage of DLCO |
| No-Donor Arm | Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline | 0 percentage of DLCO |
Comparison: This is the result comparing DLCO changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.37Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline | 9.5 percentage of ERV |
| No-Donor Arm | Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline | -2 percentage of ERV |
Comparison: This is the result comparing ERV changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.268Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline | 2.5 percentage of FEV1 |
| No-Donor Arm | Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline | 0.0 percentage of FEV1 |
Comparison: This is the result comparing FEV1 changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.596Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline | 1.5 percentage of FVC |
| No-Donor Arm | Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline | 0.0 percentage of FVC |
Comparison: This is the result comparing FVC changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.684Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline | 3 percentage of FRC |
| No-Donor Arm | Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline | -3.5 percentage of FRC |
Comparison: This is the result comparing FRC changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.832Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline | -1 percentage of IC |
| No-Donor Arm | Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline | -4.5 percentage of IC |
Comparison: This is the result comparing IC changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: >0.999Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Oxygen Saturation From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Oxygen Saturation From Baseline | 1 percentage of oxygen saturation |
| No-Donor Arm | Change in Pulmonary Function of Oxygen Saturation From Baseline | 0 percentage of oxygen saturation |
Comparison: This is the result comparing oxygen saturation changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.094Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline | 0.5 percentage of FEV1/FVC |
| No-Donor Arm | Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline | 0.5 percentage of FEV1/FVC |
Comparison: This is the result comparing FEV1/FVC changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.863Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Residual Volume (RV) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Residual Volume (RV) From Baseline | 6 percentage of RV |
| No-Donor Arm | Change in Pulmonary Function of Residual Volume (RV) From Baseline | -11 percentage of RV |
Comparison: This is the result comparing RV changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.241Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline | -1.0 percentage of TLC |
| No-Donor Arm | Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline | 0 percentage of TLC |
Comparison: This is the result comparing TLC changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.767Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Function of Vital Capacity (VC) From Baseline
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.
Time frame: Baseline, 2 years
Population: Analysis population includes participants that are biologically assigned to different arms and completed both baseline and 2-year assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Pulmonary Function of Vital Capacity (VC) From Baseline | 0.5 percentage of VC |
| No-Donor Arm | Change in Pulmonary Function of Vital Capacity (VC) From Baseline | 2 percentage of VC |
Comparison: This is the result comparing VC changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.455Wilcoxon (Mann-Whitney)
Secondary
Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline | 0.1 meters per second (m/s) |
| No-Donor Arm | Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline | 0.05 meters per second (m/s) |
Comparison: This is the result comparing TRJV from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.636Wilcoxon (Mann-Whitney)
Secondary
Frequencies of Infections
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.
Time frame: 2 years
Population: Using the intent-to-treat principle, participants remained in their assigned treatment arm regardless of treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donor Arm | Frequencies of Infections | Epstein-Barr Virus | 3 infection |
| Donor Arm | Frequencies of Infections | Staphylococcus | 0 infection |
| Donor Arm | Frequencies of Infections | Staphylococcus (NOS) | 2 infection |
| Donor Arm | Frequencies of Infections | Respiratory Syncytial virus | 1 infection |
| Donor Arm | Frequencies of Infections | Staphylococcus (coag -) | 2 infection |
| Donor Arm | Frequencies of Infections | Clostridium difficile | 4 infection |
| Donor Arm | Frequencies of Infections | Escherichia coli | 3 infection |
| Donor Arm | Frequencies of Infections | Other Bacteria | 2 infection |
| Donor Arm | Frequencies of Infections | Cytomegalovirus | 2 infection |
| Donor Arm | Frequencies of Infections | Gram Negative Rod (NOS) | 0 infection |
| Donor Arm | Frequencies of Infections | Influenza | 1 infection |
| Donor Arm | Frequencies of Infections | Rhinovirus | 2 infection |
| Donor Arm | Frequencies of Infections | Klebsiella | 0 infection |
| Donor Arm | Frequencies of Infections | Human Herpes Virus - 6 | 2 infection |
| Donor Arm | Frequencies of Infections | Pseudomonas | 0 infection |
| Donor Arm | Frequencies of Infections | Streptococcus | 1 infection |
| Donor Arm | Frequencies of Infections | Bacillus | 0 infection |
| Donor Arm | Frequencies of Infections | Herpes Zoster | 2 infection |
| Donor Arm | Frequencies of Infections | Enterococcus | 0 infection |
| Donor Arm | Frequencies of Infections | Other Viral | 5 infection |
| Donor Arm | Frequencies of Infections | Staphylococcus (coag +) | 1 infection |
| No-Donor Arm | Frequencies of Infections | Staphylococcus | 1 infection |
| No-Donor Arm | Frequencies of Infections | Herpes Zoster | 0 infection |
| No-Donor Arm | Frequencies of Infections | Clostridium difficile | 2 infection |
| No-Donor Arm | Frequencies of Infections | Human Herpes Virus - 6 | 0 infection |
| No-Donor Arm | Frequencies of Infections | Staphylococcus (coag +) | 0 infection |
| No-Donor Arm | Frequencies of Infections | Respiratory Syncytial virus | 0 infection |
| No-Donor Arm | Frequencies of Infections | Other Bacteria | 0 infection |
| No-Donor Arm | Frequencies of Infections | Rhinovirus | 0 infection |
| No-Donor Arm | Frequencies of Infections | Streptococcus | 0 infection |
| No-Donor Arm | Frequencies of Infections | Other Viral | 2 infection |
| No-Donor Arm | Frequencies of Infections | Epstein-Barr Virus | 0 infection |
| No-Donor Arm | Frequencies of Infections | Staphylococcus (NOS) | 0 infection |
| No-Donor Arm | Frequencies of Infections | Staphylococcus (coag -) | 1 infection |
| No-Donor Arm | Frequencies of Infections | Escherichia coli | 1 infection |
| No-Donor Arm | Frequencies of Infections | Cytomegalovirus | 0 infection |
| No-Donor Arm | Frequencies of Infections | Influenza | 0 infection |
| No-Donor Arm | Frequencies of Infections | Klebsiella | 1 infection |
| No-Donor Arm | Frequencies of Infections | Pseudomonas | 1 infection |
| No-Donor Arm | Frequencies of Infections | Bacillus | 1 infection |
| No-Donor Arm | Frequencies of Infections | Enterococcus | 1 infection |
| No-Donor Arm | Frequencies of Infections | Gram Negative Rod (NOS) | 1 infection |
Secondary
Frequencies of Sickle Cell Disease (SCD) Events of Special Interest
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.
Time frame: 2 Years
Population: Using the intent-to-treat principle, participants remained in their assigned treatment arm regardless of treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Any event leading to an advanced care setting or intensive care unit admission/transfer at 2 yrs | 1 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Any event leading to an advanced care setting or intensive care unit admission/transfer at 1 yr | 5 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Avascular necrosis at 1 yr | 4 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Pulmonary hypertension at 2 yrs | 1 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Significant cerebrovascular event including stroke, transient ischemic attack, and seizure at 1 yr | 8 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Significant cerebrovascular event including stroke, transient ischemic attack, and seizure at 2 yrs | 1 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Leg ulceration at 1 yr | 1 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Renal function compromise at 2 yrs | 4 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Pulmonary hypertension at 1 yr | 1 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Avascular necrosis at 2 yrs | 1 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Acute chest syndrome with hospitalization at 1 yr | 3 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Leg ulceration at 2 yrs | 0 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Renal function compromise at 1 yr | 7 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Acute chest syndrome with hospitalization at 2 yrs | 0 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Vaso-occlusive pain w/ hospitalization or parenteral opioid drugs in outpatient setting at 1 yr | 11 event |
| Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Vaso-occlusive pain w/ hospitalization or parenteral opioid drugs in outpatient setting at 2 yrs | 3 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Vaso-occlusive pain w/ hospitalization or parenteral opioid drugs in outpatient setting at 1 yr | 161 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Any event leading to an advanced care setting or intensive care unit admission/transfer at 2 yrs | 6 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Pulmonary hypertension at 1 yr | 6 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Significant cerebrovascular event including stroke, transient ischemic attack, and seizure at 1 yr | 4 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Renal function compromise at 1 yr | 14 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Avascular necrosis at 1 yr | 11 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Leg ulceration at 1 yr | 4 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Acute chest syndrome with hospitalization at 1 yr | 18 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Vaso-occlusive pain w/ hospitalization or parenteral opioid drugs in outpatient setting at 2 yrs | 144 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Any event leading to an advanced care setting or intensive care unit admission/transfer at 1 yr | 5 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Pulmonary hypertension at 2 yrs | 7 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Significant cerebrovascular event including stroke, transient ischemic attack, and seizure at 2 yrs | 6 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Renal function compromise at 2 yrs | 8 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Avascular necrosis at 2 yrs | 8 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Leg ulceration at 2 yrs | 1 event |
| No-Donor Arm | Frequencies of Sickle Cell Disease (SCD) Events of Special Interest | Acute chest syndrome with hospitalization at 2 yrs | 10 event |
Comparison: This is the result comparing severe vaso-occlusive pain (VOC) with hospitalization or parenteral opioid drugs in outpatient setting between two biologically assigned arms during the first year after biologic assignment. The null hypothesis is that there is no difference in biologically assigned arms during the first year after assignment.p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: This is the result comparing significant cerebrovascular event between two biologically assigned arms during the first year after biologic assignment. Significant cerebrovascular event includes stroke, transient ischemic attack, and seizure. The null hypothesis is that there is no difference in biologically assigned arms during the first year after assignment.p-value: 0.027Wilcoxon (Mann-Whitney)
Comparison: This is the result comparing severe Vaso-occlusive pain (VOC) with hospitalization or parenteral opioid drugs in outpatient setting between two biologically assigned arms during the second year after biologic assignment. The null hypothesis is that there is no difference in biologically assigned arms during the second year after assignment.p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline | -0.08 units on a scale |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline | -0.25 units on a scale |
Comparison: This is the result comparing 28-Day Pain Diary Average Pain Intensity changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.649Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline | 0 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline | 0 T-score |
Comparison: This is the result comparing Anxiety changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.343Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline | -1 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline | 1 T-score |
Comparison: This is the result comparing ASCQ-Me Stiffness changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.207Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline | 0 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline | 0 T-score |
Comparison: This is the result comparing Depression changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.491Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline | -13 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline | 0 T-score |
Comparison: This is the result comparing fatigue score changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline | -0.5 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline | 0 T-score |
Comparison: This is the result comparing Pain Intensity changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.146Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline | -12 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline | -1 T-score |
Comparison: This is the result comparing pain interference score changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.071Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline | 15 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline | 2 T-score |
Comparison: This is the result comparing social roles score changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline | 5 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline | 1 T-score |
Comparison: This is the result comparing Physical Function changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.242Wilcoxon (Mann-Whitney)
Secondary
Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline
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.
Time frame: Baseline, 2 years
Population: Participants that are biologically assigned to different arms and that completed both the baseline and 2-year assessment; this follows the intent-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Donor Arm | Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline | 1 T-score |
| No-Donor Arm | Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline | 0 T-score |
Comparison: This is the result comparing Sleep Disturbance changes from 2 years after biologic assignment to baseline between two biologically assigned arms. The null hypothesis is that there is no difference between biologically assigned armsp-value: 0.594Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Primary and Secondary Graft Failure
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.
Time frame: 2 years
Population: Analysis population includes transplanted participants who were biologically assigned to donor arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donor Arm | Number of Participants With Primary and Secondary Graft Failure | Primary graft failure | 0 participants |
| Donor Arm | Number of Participants With Primary and Secondary Graft Failure | Secondary graft failure | 3 participants |
Secondary
Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment
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.
Time frame: Day 600 after biological assignment
Population: Patients who enrolled on the donor arm and received transplant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Donor Arm | Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment | 30 percentage of participants |
| No-Donor Arm | Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment | 57 percentage of participants |
Comparison: The null hypothesis is that there is no difference of chronic GVHD in patients who received different donor type at transplantp-value: 0.233Gray's test for cumulative Incidence
Secondary
Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment
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.
Time frame: 180 days after biological assignment
Population: Patients who enrolled on the donor arm and received transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Donor Arm | Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment | 30 percentage of participants |
| No-Donor Arm | Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment | 46 percentage of participants |
Comparison: The null hypothesis is that there is no difference of grade II-IV acute GVHD in patients who received different donor type at transplantp-value: 0.313Gray's test for cumulative Incidence