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Completed

NCT Number: NCT02766465

Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503)

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.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

15 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Benioff Children's Hospital at Oakland, Oakland, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥ 15 and < 41 years
  • 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):
  • Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours;
  • 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);
  • 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.
  • 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)
  • An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
  • 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.

  • Adequate physical function as measured by all of the following:
  • Karnofsky/Lansky performance score ≥ 60
  • Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition Scan (MUGA).
  • 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:

  • 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
  • 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

  • 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).
  • 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
  • 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

  • HLA typing with a donor search prior to referral (consultation with HCT physician).
  • 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.
  • 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.
  • 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.
  • Subjects with a known HLA-identical sibling or HLA-matched unrelated donor are excluded
  • Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
  • Seropositivity for HIV.
  • Previous HCT or solid organ transplant.
  • Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
  • A history of substance abuse as defined by version IV of the Diagnostic & Statistical Manual of Mental Disorders (DSM IV).
  • Demonstrated lack of compliance with prior medical care as determined by referring physician.
  • Pregnant or breast feeding females.
  • Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy.

Treatment and study plan

busulfan

Drug

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.

Other names: Busulfex

Fludarabine

Drug

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

Other names: Fludara

r-ATG

Drug

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).

Other names: Rabbit antithymocyte globulin

Hematopoietic Cell Transplant

Procedure

A,B,C:

Day 0 is the day of transplantation.

Other names: Bone Marrow Transplant; BMT; HCT

Tacrolimus

Drug

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

Other names: Prograf®

methotrexate

Drug

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

Other names: MTX

Standard of care

Procedure

Continue to receive standard of care treatment per patient's SCD physician.

Alemtuzumab

Drug

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.

Other names: Lemtrada

Total Body Irradiation (TBI)

Drug

Total Body Irradiation 300 cGY on Day -2

sirolimus

Drug

Sirolimus at therapeutic doses through day 180, then taper per institutional guidelines if donor CD3+ >50%

Other names: Rapamune

melphalan

Drug

C:

Melphalan 140 mg/m2 IV dose will be given on Day -3

Other names: Alkeran

G-CSF

Drug

G-CSF 5 μg/kg/day continue until neutrophil engraftment.

Other names: Granulocyte colony-stimulating factor

Primary outcomes

  1. Percentage of Participants With Overall Survival (OS) at 2 Years After Biologic Assignment

    Time frame: 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 outcomes

  1. Frequencies of Sickle Cell Disease (SCD) Events of Special Interest

    Time frame: 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.

  2. Change in 6-minute Walk Distance (6MWD) Assessment From Baseline

    Time frame: 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.

  3. Change in Transcuspid Regurgitant Jet Velocity (TRJV) Assessment From Baseline

    Time frame: 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.

  4. Change in Albuminuria Assessment From Baseline

    Time frame: 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.

  5. Health-Related Quality of Life (HRQoL) Component Physical Function Changes From Baseline

    Time frame: 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.

  6. Health-Related Quality of Life (HRQoL) Component Anxiety Changes From Baseline

    Time frame: 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.

  7. Health-Related Quality of Life (HRQoL) Component Depression Changes From Baseline

    Time frame: 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.

  8. Health-Related Quality of Life (HRQoL) Component Fatigue Score Changes in From Baseline

    Time frame: 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.

  9. Health-Related Quality of Life (HRQoL) Component Sleep Disturbance Changes From Baseline

    Time frame: 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.

  10. Health-Related Quality of Life (HRQoL) Component Participation in Social Roles Score Changes From Baseline

    Time frame: 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.

  11. Health-Related Quality of Life (HRQoL) Component Pain Interference Score Changes From Baseline

    Time frame: 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.

  12. Health-Related Quality of Life (HRQoL) Component Pain Intensity Changes From Baseline

    Time frame: 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.

  13. Health-Related Quality of Life (HRQoL) Component 28-Day Pain Diary Average Pain Intensity Changes From Baseline

    Time frame: 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.

  14. Health-Related Quality of Life (HRQoL) Component ASCQ-Me Stiffness Changes From Baseline

    Time frame: 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.

  15. Change in Pulmonary Function of Forced Expiratory Volume 1 Second (FEV1) From Baseline

    Time frame: 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.

  16. Change in Pulmonary Function of Forced Vital Capacity (FVC) From Baseline

    Time frame: 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.

  17. Change in Pulmonary Function of Ratio of FEV1 to FVC (FEV1/FVC) From Baseline

    Time frame: 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.

  18. Change in Pulmonary Function of Vital Capacity (VC) From Baseline

    Time frame: 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.

  19. Change in Pulmonary Function of Total Lung Capacity (TLC) From Baseline

    Time frame: 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.

  20. Change in Pulmonary Function of Residual Volume (RV) From Baseline

    Time frame: 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.

  21. Change in Pulmonary Function of Expiratory Reserve Volume (ERV) From Baseline

    Time frame: 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.

  22. Change in Pulmonary Function of Inspiratory Capacity (IC) From Baseline

    Time frame: 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.

  23. Change in Pulmonary Function of Functional Residual Capacity (FRC) From Baseline

    Time frame: 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.

  24. Change in Pulmonary Function of Diffusing Capacity for Carbon Monoxide (DLCO) From Baseline

    Time frame: 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.

  25. Change in Pulmonary Function of Oxygen Saturation From Baseline

    Time frame: 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.

  26. Frequencies of Infections

    Time frame: 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.

  27. Percentage of Participants With Grades II-IV Acute GVHD at Day 180 After Biological Assignment

    Time frame: 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.

  28. Percentage of Participants With Chronic GVHD at Day 600 After Biological Assignment

    Time frame: 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.

  29. Number of Participants With Primary and Secondary Graft Failure

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Medical College of Wisconsin

Other

Collaborators

  • Blood and Marrow Transplant Clinical Trials Network
  • Dana-Farber Cancer Institute
  • Emory University
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Marrow Donor Program

Registry information

Official study title

A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults With Severe Sickle Cell Disease (BMT CTN 1503)

Acronym: STRIDE2

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
May 9, 2016
Registry last updated
Apr 18, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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