Minimizing Toxicity in HLA-identical Sibling Donor Transplantation for Children With Sickle Cell Disease

Summary

This multisite prospective study seeks to determine if HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus (Sickle transplant Using a Nonmyeloablative approach, "SUN") can decrease the toxicity of transplant while achieving a high cure rate for children with sickle cell disease (SCD).

Conditions

• Sickle Cell Disease

Interventions

DRUG

Alemtuzumab, low dose total body irradiation, Sirolimus

The conditioning regimen (SUN regimen) will consist of alemtuzumab daily for 5 days (total dose 1 mg/kg) and low dose total body irradiation (TBI) 300 cGY on Day -2 with gonadal shielding if possible. The HSCT graft will be G-CSF mobilized PBSCs with minimum CD34+ of 5 x106/kg recipient weight, goal of 10 x 106/kg (no upper limit). A peripheral blood stem cell (PBSC) graft was selected as it engrafts faster than bone marrow and would lead to shorter period of neutropenia and infection and less thrombocytopenia and need for platelet transfusion. GVHD prophylaxis will be sirolimus with a loading dose 3 mg/m2 on day -1. Sirolimus will be continued at 1 mg/m2/day starting on day 0 and dose adjusted to maintain a target trough level 5-15 ng/mL for the first 3 months and 5-10 ng/mL for the remainder of the first year.

Sponsors & Collaborators

• The Hospital for Sick Children

  collaborator OTHER

• Levine Children's Hospital

  collaborator OTHER

• Ann & Robert H Lurie Children's Hospital of Chicago

  collaborator OTHER

• Nationwide Children's Hospital

  collaborator OTHER

• Columbia University

  collaborator OTHER

• The Children's Hospital at Montefiore

  collaborator OTHER

• Alberta Children's Hospital

  collaborator OTHER

• Robert Nickel

  lead OTHER

Principal Investigators

• Robert Nickel, MD · Children's National Research Institute

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-04-17

Primary Completion

2030-11-30

Completion

2030-11-30

FDA Drug

Yes

Countries

• United States
• Canada

Study Locations