Haploidentical PBMC Transplant for Severe Congenital Anemias

Summary

Background:

Bone marrow transplantation (BMT), which involves transplanting a donor's marrow stem cells, is capable of curing some congenital anemias. BMT usually involves high-intensity treatment with chemotherapy and radiation to kill abnormal cells, which affects all systems of the body.

People with anemias often have damage to other organs such as the kidneys, which can be further damaged by the chemotherapy. Only approximately 20 percent of patients have a full-matched donor, making treatment for many people with anemias unavailable. However, 90 percent of patients may have a half-matched donor, but using a half-matched donor increases the toxicity of BMT.

Objectives:

To determine if a research BMT with half-matched donor cells, low-intensity radiation, immunosuppressant drugs, and no chemotherapy will be effective in patients with sickle cell disease and Beta-thalassemia.

To determine the effectiveness of cyclophosphamide, an immunosuppressant drug, in preventing rejection of the donor cells.

Eligibility:

Recipients are individuals at least 18 years of age who have been diagnosed with sickle cell disease and Beta-thalassemia, and who have a family member who is a haploidentical (i.e., half match) tissue match.

Donors are healthy individuals between the ages of 2 and 80 who are found to be suitable donors.

Design:

Donors will undergo apheresis, which involves withdrawing blood from one arm vein, passing it through a machine that removes bone marrow stem cells, and returning the remaining blood through the vein in the other arm. Donors will receive a drug that causes the stem cells to be released into the bloodstream prior to the apheresis procedure.

Recipients will undergo routine physical and laboratory examinations, including bone marrow sampling at the beginning of the study. After transplantation, physical and laboratory examinations will occur on a weekly or twice weekly basis at the outpatient clinic. Recipients will be examined every 6 months starting 100 days posttransplant for 5 years.

Recipients will receive low-dose radiation in two treatments 1 and 2 days before the transplant. They will also be given immunosuppressant therapy with alemtuzumab and sirolimus. Another immunosuppressant drug, cyclophosphamide, will be given in the future as needed to subsets of the recipients to prevent rejection of donor cells.

Recipients will receive the donor stem cells through a previously inserted central line. The process takes up to 8 hours.

Recipients will receive blood transfusions as necessary to prevent anemia and bleeding during the posttransplant period. They may also receive intravenous antibiotics to prevent infection.

Conditions

• Sickle Cell Anemia

Interventions

PROCEDURE

PBSC Transplant

PBSC transplant

DRUG

Alemtuzumab

alemtuzumab

DRUG

Sirolimus

sirolimus

DRUG

Cyclophosphamide

cyclophosphamide

PROCEDURE

Low Dose Irradiation

low dose irradiation

Sponsors & Collaborators

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

  lead NIH

Principal Investigators

• Courtney D Fitzhugh, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

2 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-12-14

Primary Completion

2018-08-01

Completion

2026-09-10

FDA Drug

Yes

Countries

• United States

Study Locations