Treatment of Sickle Cell Anemia With Stem Cell Transplant

Summary

This is a clinical research trial in which a novel preparatory regimen was developed for bone marrow transplant (BMT) which eliminates the primary obstacle to transplant, the lack of a matched sibling donor. It is believed this regimen is sufficiently efficacious and sufficiently gentle to apply to patients with sickle cell anemia and related disorders. It is proposed to characterize the efficacy and toxicity of this regimen in high risk patients with sickle cell anemia using criteria for patient selection that have been accepted in prior BMT trials in patients with sickle cell disease, specifically only the subset of patients whose prior clinical behavior indicates that they are at high risk for serious morbidity and early mortality. In addition, it is proposed to characterize the pathophysiology of a consistent febrile response seen in the haploidentical BMT regimen the investigators have developed at Thomas Jefferson University (TJU).

The primary goal of this study is to determine the response rate to a reduced intensity conditioning regimen which consists of fludarabine, cytarabine, low dose total body irradiation and cyclophosphamide in patients with severe sickle cell anemia.

Conditions

• Sickle Cell Anemia
• Sickle Cell-hemoglobin C Disease
• Sickle Cell-β0-thalassemia

Interventions

DRUG

Fludarabine

Subjects will receive fludarabine at a dose of 30 mg/m2 daily for 4 days as part of the preparative regimen

DRUG

Cytarabine

Subjects will receive cytarabine at a dose of 2 g/m2 daily for 4 days, approximately 4 hours after the fludarabine

DEVICE

Cellular Infusions

Subjects will receive the cellular product in 2 steps. The first is a lymphocyte infusion of 2 X 10e8 lymphocytes/kg on the day they receive total body irradiation. The second is a CD34 enriched stem cell product approximately 48 hours after the cyclophosphamide. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.

RADIATION

Total Body Irradiation

All subjects will receive 200cGy TBI in a single fraction on the AM they receive the lymphocyte infusion

DRUG

Cyclophosphamide

All subjects will receive cyclophosphamide at a dose of 60 mg/kg at approximately 72 and 96 hours after the lymphocyte infusion

DRUG

Bortezomib

Subjects will receive bortezomib 1.3 mg/kg on Day 1,4,8, and 11 of a 21 day cycle. This will be repeated for 2 cycles.

DRUG

Rituximab

Subjects will receive rituximab 375 mg/m2 on day 1 and day 8 of a 21 day cycle, on days they will also be receiving rituximab. This will be repeated for 2 cycles.

PROCEDURE

Plasmapheresis

Subjects who continue to have detectable anti-donor antibody will receive plasmapheresis to reduce the antibody further

Sponsors & Collaborators

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

  collaborator NIH

• Sidney Kimmel Cancer Center at Thomas Jefferson University

  lead OTHER

Principal Investigators

• Joanne Filicko-O'Hara, MD · Thomas Jefferson University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-09-30

Primary Completion

2011-08-31

Completion

2011-08-31

Countries

• United States

Study Locations