NCT02766465

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 138 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 15 Years – 40 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Sickle Cell Disease

Interventions

Type	Name	Description
DRUG	Busulfan	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.
DRUG	Fludarabine	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
DRUG	r-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).
PROCEDURE	Hematopoietic Cell Transplant	A,B,C: Day 0 is the day of transplantation.
DRUG	Tacrolimus	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
DRUG	Methotrexate	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
PROCEDURE	Standard of Care	Continue to receive standard of care treatment per patient's SCD physician.
DRUG	Alemtuzumab	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.
DRUG	Total Body Irradiation (TBI)	Total Body Irradiation 300 cGY on Day -2
DRUG	Sirolimus	Sirolimus at therapeutic doses through day 180, then taper per institutional guidelines if donor CD3+ \>50%
DRUG	Melphalan	C: Melphalan 140 mg/m2 IV dose will be given on Day -3
DRUG	G-CSF	G-CSF 5 μg/kg/day continue until neutrophil engraftment.

Timeline

• Start date: 2017-03-16
• Primary completion: 2023-05-02
• Completion: 2023-08-02
• First posted: 2016-05-09
• Last updated: 2025-04-18
• Results posted: 2024-09-24

Locations

35 sites across 1 country: United States

Regulatory

• FDA-regulated drug study