Bone Marrow Transplantation vs Standard of Care in Patients With Severe Sickle Cell Disease (BMT CTN 1503) (STRIDE2)
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|ClinicalTrials.gov Identifier: NCT02766465|
Recruitment Status : Recruiting
First Posted : May 9, 2016
Last Update Posted : May 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Drug: Busulfan Drug: Fludarabine Drug: r-ATG Procedure: Bone Marrow Transplant Drug: Tacrolimus Drug: Methotrexate Procedure: Standard of Care||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults With Severe Sickle Cell Disease (BMT CTN #1503)|
|Actual Study Start Date :||November 2016|
|Estimated Primary Completion Date :||March 2022|
|Estimated Study Completion Date :||March 2023|
Experimental: Donor Arm
The donor arm will be treated with a preparative regimen of busulfan, fludarabine, and r-ATG before undergoing the bone marrow transplant. Graft-vs-Host-Disease (GVHD) prophylaxis will be tacrolimus combined with methotrexate.
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 Name: Busulfex
Fludarabine dose will be 35 mg/m^2/day administered IV on days -7 through -3 (total fludarabine dose is 175 mg/m^2).
Other Name: Fludara
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 Name: Rabbit antithymocyte globulin
Procedure: Bone Marrow Transplant
Day 0 is the day of bone marrow transplantation.
Other Name: Hematopoietic Cell Transplant; BMT; HCT
Tacrolimus commences on day -3 and extends through day +180 after transplantation with doses adjusted to maintain appropriate levels according to institutional guidelines.
Other Name: Prograf®
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.
Other Name: MTX
Active Comparator: No-Donor Arm
No-donor arm will continue with standard of care per their SCD physician.
Procedure: Standard of Care
Continue to receive standard of care treatment per patient's SCD physician.
- Overall Survival (OS) [ Time Frame: 2 Years ]OS will be compared between treatment arms using a point-wise comparison at 2-years, and the survival curves will be estimated using the Kaplan Meier product limit estimator.
- Occurrence of Sickle Cell Disease (SCD) related events [ Time Frame: 2 Years ]Examination of the occurrence of the SCD-related events will be performed. Exact logistic regression will be used to estimate an odds ratio of each of these events between treatment groups, assuming that at least one event occurs on study in each of the treatment groups, controlling for other patient related characteristics and individual history of the event of interest.
- Mean Pain Intensity [ Time Frame: Day 28, 1 year, and 2 years ]Mean pain intensity assessed by an electronic pain diary.
- Exercise Capacity [ Time Frame: Day 28, 1 year, and 2 years ]The 6-minute walk distance (6MWD) test will be used to assess exercise capacity.
- Cardiac Function [ Time Frame: Day 28, 1 year, and 2 years ]Cardiac function will be assessed by the change from baseline in Tricuspid regurgitant jet velocity (TRJV).
- Pulmonary Function [ Time Frame: Day 28, 1 year, and 2 years ]Pulmonary function will be assessed by the change from baseline in Forced Expiratory Volume 1 second (FEV1).
- Renal Function [ Time Frame: Day 28, 1 year, and 2 years ]Renal function will be assessed through measurements of albuminuria (urine-albumin creatinine ratio) and serum creatinine.
- Health-Related Quality of Life (HRQoL) [ Time Frame: Day 28, 1 year, and 2 years ]HRQoL assessed using the NIH's PROMIS 57 instrument.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02766465
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|Study Director:||Mary Eapen, MD||Center for International Blood and Marrow Transplant Research|