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

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.

Conditions

• Sickle Cell Disease

Interventions

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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Blood and Marrow Transplant Clinical Trials Network

  collaborator NETWORK

• Dana-Farber Cancer Institute

  collaborator OTHER

• National Marrow Donor Program

  collaborator OTHER

• Emory University

  collaborator OTHER

• Medical College of Wisconsin

  lead OTHER

Principal Investigators

• Mary Eapen, MD · Center for International Blood and Marrow Transplant Research

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-03-16

Primary Completion

2023-05-02

Completion

2023-08-02

FDA Drug

Yes

Countries

• United States

Study Locations