Treatment of Sickle Cell Anemia With Stem Cell Transplant

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - 45 Years

Healthy Volunteers

Not accepted

Interventions

• Fludarabine — DRUG
  Subjects will receive fludarabine at a dose of 30 mg/m2 daily for 4 days as part of the preparative regimen
• Cytarabine — DRUG
  Subjects will receive cytarabine at a dose of 2 g/m2 daily for 4 days, approximately 4 hours after the fludarabine
• Cellular Infusions — DEVICE
  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.
• Total Body Irradiation — RADIATION
  All subjects will receive 200cGy TBI in a single fraction on the AM they receive the lymphocyte infusion
• Cyclophosphamide — DRUG
  All subjects will receive cyclophosphamide at a dose of 60 mg/kg at approximately 72 and 96 hours after the lymphocyte infusion
• Bortezomib — DRUG
  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.
• Rituximab — DRUG
  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.
• Plasmapheresis — PROCEDURE
  Subjects who continue to have detectable anti-donor antibody will receive plasmapheresis to reduce the antibody further

Study Details

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.

Key Dates

Start date

Sep 30, 2009

Status verified

May 2025

Primary completion

Aug 31, 2011

Completion

Aug 31, 2011

Study Design

Enrollment

2 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: HSCT
  Subjects receive the preparative regimen in 2 steps. The "first step" will be with fludarabine and cytarabine and a low dose of total body irradiation. This will be followed by the "first step" of the transplant graft - the donor lymphocytes. The "second step" of the chemotherapy will be two doses of cyclophosphamide. This will then be followed by the "second step" of the transplant graft - the stem cells. Only subjects with prior alloimmunization against donor will receive desensitization. Subjects who demonstrate alloimmunization against the HLA of the donor will receive bortezomib and rituximab in combination with plasmapheresis prior to the admission for transplant.

Primary Outcome Measure

Stable Engraftment [ Time Frame: 180 days post-infusion ]

Locations (1)

Find similar trials in Philadelphia, PA

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