Donor Stem Cell Transplantation for Congenital Immunodeficiencies

Summary

This study uses transplantation to treat patients with problems in their immune system. The immune system cells come from the bone marrow where they grow from special cells called stem cells. Giving patients stem cells from someone else may help to cure many patients with certain immune diseases. This is called 'bone marrow transplantation'. This procedure can have side effects that are life-threatening. To try to make transplantation safer we are using lower doses of the medications used in preparing the patient for the transplant.

'Conditioning' treatments are given to patients to create space in their bone marrow. This lets the cells of the donor go into the bone marrow and produce normal immune cells. This study will use lower doses of a drug called busulfan and lower doses of radiation than what are currently being used in other kinds of bone marrow transplantation for other diseases.

Another problem that can occur with bone marrow transplantation is 'graft-versus-host disease'. This happens when the cells of the donor attacks different parts of the patient s body. This study will use a medicine called sirolimus instead of the usual medicine, cyclosporine, to prevent graft-versus-host disease.

To go onto this study, you must have:

1. A severe immune deficiency, such as chronic granulomatous disease or leukocyte adhesion deficiency.
2. Have problems from the disease that call for stem cell transplantation.
3. You must also be between the ages of 2 and 40 years.

Two groups of patients are included in this study:

1. Patients who have a brother or sister that have stem cells that match the patient. This is known as an allogeneic matched sibling transplant.
2. Patients who do not have a matched sibling donor but have a donor that matches in the National Marrow Donor Program. This is know as matched unrelated donor transplantation.

Patients will have the following procedures:

* To create space in the bone marrow, patients are given two drugs, Campath-1H and busulfan. To prevent the body from getting rid of the donated cells, patients are given sirolimus. On the day before the BMT, patients in the matched unrelated donor group also receive a low-dose of whole-body radiation. This will further improve the chances that the patients body will accept the donor cells.
* Patients will get the donor stem cells through an intravenous (IV) line that goes into a vein in their body. The cells make their way to the bone marrow space and slowly refill the marrow over the next several weeks. Patients will usually stay in the hospital for 30 days after the transplant.
* For the first 3 months after the transplant, patients are watched closely. The patients will have frequent visits to the clinic. During these visits the patient will have a physical examination and blood tests. The doctor and nurse will also check any symptoms the patient may have. At day 100 after the transplant a sample of bone marrow is taken.
* Patients will continue to be followed periodically for at least 5 years after the transplant.

Conditions

• Inherited Immune Deficiencies

Interventions

DRUG

Campath 1H

Conditioning with Campath 1 mg/kg total dose given intravenously over 5 days

DRUG

Busulfan

Busulfan 5-10 mg/kg total dose given intravenously over 2 days based on patient underlining immune deficiency disorder

DRUG

Horse Anti-human Thymocyte Globulin (h-ATG)

Conditioning with h-ATG 40 mg/kg total dose over 4 days given intravenously

DRUG

Total Body Irradiation (TBI)

TBI 200 - 300 centigray (cGy) in two fractions at day -2 or same day depending on patient underlining immune deficiency disorder

DRUG

Sirolimus or equivalent based on response

post Transplantation immunosuppressants

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Elizabeth M Kang, M.D. · National Institute of Allergy and Infectious Diseases (NIAID)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

2 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-01-19

Primary Completion

2019-11-01

Completion

2019-11-01

FDA Drug

Yes

Countries

• United States

Study Locations