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Protocol Details

Allogeneic and Matched Unrelated Donor Stem Cell Transplantation for Congenital Immunodeficiencies or Patients with Autoinflammatory/Immunodysregulatory Conditions: Busulfan-Based Conditioning with Campath- 1H or h-ATG, Radiation, and Sirolimus

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 2
Max Age: 65

Referral Letter Required


Population Exclusion(s)


Special Instructions

Currently Not Provided


MUD Transplant;
HLA Matched Transplant;

Recruitment Keyword(s)

Congenital Immunodeficiency;
Bone Marrow Transplant


Inherited Immune Deficiencies

Investigational Drug(s)


Investigational Device(s)



Drug: Fludarabine
Drug: Total Body Irradiation, Busulfan, Campath-1H, or h-ATG, Fludarabine
Drug: Sirolimus or equivalent based on response
Drug: Granulocyte Colony Stimulating Factor (G-CSF)
Other: hematopoietic progenitor cells

Supporting Site

National Institute of Allergy and Infectious Diseases

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 3 and 65 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.

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Must have a confirmed congenital immunodeficiency or Autoinflammatory/immunodysregulatory Condition.

Must have sufficient complications from underlying disease to warrant undergoing transplantation.

Ages 2 years 65 years.

HLA-matched family donor available or an HLA matched unrelated PBSC graft (10/10 or 9/10 mismatch) available, or a minimum of 4/6 HLA matched cord blood product. (If the size of the cord blood graft is less than 3.0 x 10(7) cells, a second appropriate 4/6 or greater match cord blood product must be available).

Must be HIV negative.

Must be able to stay within one hour s travel of the NIH for the first 3 months after transplantation and have a family member or other designated companion to stay with during the post transplant period.

Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance to NIH -200 NIH Durable Power of Attorney for Health Care Decision Making.

If of child-bearing potential, must agree to consistently use contraception throughout study participation and for 3 months post-study. Acceptable forms of contraception are:

-Condoms, male or female, with or without a spermicide

-Diaphragm or cervical cap with spermicide

-Intrauterine device

-Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA-approved contraceptive method

-Male partner has previously undergone a vasectomy


HLA-matched (i.e., 6 of 6 alleles identical) family donor.

Ages greater than or equal to 2 years and weight greater than or equal to 18 kg (in so far that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor with no more than 2 aphereses).

Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive, and no history of stroke).

Must be HIV, hepatitis and syphilis negative.

* Inclusion criteria for donors for matched unrelated products from the National Marrow Donor Program is done per NMDP protocol.



Eastern Cooperative Oncology Group (ECOG) or equivalent performance status of 3 or more (See Supportive Care guidelines, available at

Left ventricular ejection fraction less than 40%.

Transaminases greater than 5 times upper limit of normal based on the patient s clinical situation and at the discretion of the investigator.

Psychiatric disorder or mental deficiency severe enough as to make compliance with the BMT treatment unlikely, and/or making informed consent impossible.

Major anticipated illness or organ failure incompatible with survival from AlloPBSC transplant.

Pregnant or lactating.

HIV positive.

Uncontrolled seizure disorder.

Patients who are not willing to submit their information as part of the Campath Distribution Program application or patients who the Campath Distribution Program committee has determined are not qualified to receive Campath (for patients who require Campath as part of their conditioning regimen only).


Pregnant or lactating.

Donor unfit to receive G-CSF and undergo apheresis. (e.g., uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia, signs and symptoms of acute mononucleosis).

HIV positive.

Recent exposure to infectious diseases such as chickenpox.

* Exclusion criteria for donors for matched unrelated products for the National Marrow Donor Program is done per NMDP protocol.

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Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B, Notarangelo LD, Roifman CM. Bone marrow transplantation for severe combined immune deficiency. JAMA. 2006 Feb 1;295(5):508-18.

Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May;79(3):155-69.

Johnston RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001 Jan;8(1):17-22.

Roesler J, Brenner S, Bukovsky AA, Whiting-Theobald N, Dull T, Kelly M, Civin CI, Malech HL. Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease. Blood. 2002 Dec 15;100(13):4381-90. Epub 2002 Aug 1.

Kang EM, de Witte M, Malech H, Morgan RA, Phang S, Carter C, Leitman SF, Childs R, Barrett AJ, Little R, Tisdale JF. Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome. Blood. 2002 Jan 15;99(2):698-701.

Horwitz ME, Barrett AJ, Brown MR, Carter CS, Childs R, Gallin JI, Holland SM, Linton GF, Miller JA, Leitman SF, Read EJ, Malech HL. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001 Mar 22;344(12):881-8.

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Principal Investigator

Referral Contact

For more information:

Elizabeth M. Kang, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10-CRC RM 6-3750
(301) 402-7567

Nana Kwatemaa, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 6W3750
10 Center Drive
Bethesda, Maryland 20892
(301) 451-7820

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Clinical Trials Number:


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