Bone Marrow Transplantation in Young Adults With Severe Sickle Cell Disease

Summary

This is a Phase II, single arm, multi-center trial. It is designed to estimate the efficacy and toxicity of hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD) who have high risk features.

The primary goal of this multi-center Phase II study is to determine the safety and feasibility of a conditioning regimen consisting of busulfan (Bu)/ fludarabine (Flu)/ anti-thymocyte globulin (ATG) in adult patients with severe SCD. A two-component design will be used for this study. The first component will be restricted to patients who have an HLA-identical sibling donor. Five patients will be transplanted during the first component of the study. If no more than 2 of the first 5 patients experience unacceptable toxicity, including death, within the first six months after transplantation, then the safety of the regimen will be considered promising in adult SCD patients.

The second component will include patients who have a related or an unrelated human leukocyte antigen (HLA) matched donor. Up to 15 additional patients will be transplanted in this component of the study which will evaluate the safety and feasibility of unrelated donor hematopoietic cell transplantation (HCT) in adults with SCD. Data related to study endpoints for 1 year after transplantation will be collected; however, participating centers will be encouraged to conduct long-term follow-up evaluations of patients according to standard institutional guidelines. The purpose of this pilot safety trial is to see if this approach is feasible and meets accrual goals lending support to the development of a subsequent full scale investigation of HCT and comparing outcomes in a transplantation cohort to a control cohort of adults eligible for, but unwilling or unable to receive HCT treated by supportive therapy with a primary endpoint of five years survival for this full scale comparative trial.

Conditions

• Sickle Cell Disease

Interventions

DRUG

Conditioning Regimen with Bone Marrow Transplant

The bone marrow transplant regimen is below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant. Day -8 BU 3.2 mg/ kg/dose IV Day -7 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV Day -6 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV, ATG 0.5mg/kg IV Day -5 BU 3.2 mg/kg/dose IV, FLU 35mg/m2 IV, ATG 1.0mg/kg IV Day -4 FLU 35mg/m2 IV, ATG 1.5mg/kg IV Day -3 FLU 35mg/m2 IV, ATG 1.5mg/kg IV Day -2 ATG 1.5mg/kg IV Day -1 Rest Day 0 Stem cell infusion Graft Versus Host Disease (GVHD) Regimen Day -3 Calcineurin Inhibitor (Cyclosporine or Tacrolimus) therapeutic doses through day 180, then taper Day 0 Stem cell infusion Day +1 Methotrexate 7.5 mg/m2 IV Day +3 Methotrexate 7.5 mg/m2 IV Day +6 Methotrexate 7.5 mg/m2 IV Day+11 Methotrexate 7.5 mg/m2 IV

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

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

  collaborator NIH

• Emory University

  lead OTHER

Principal Investigators

• Lakshmanan Krishnamurti, MD · Emory University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

16 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-03-31

Primary Completion

2016-06-30

Completion

2016-06-30

FDA Drug

Yes

Countries

• United States

Study Locations