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Donor Stem Cell Transplantation for Congenital Immunodeficiencies

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ) Identifier:
First received: January 23, 2007
Last updated: March 14, 2014
Last verified: February 2014

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.

Condition Intervention Phase
MUD Transplant
Congenital Immunodeficiencies
HLA Matched Transplant
Drug: Busulfan
Drug: Campath-1 H
Drug: Sirolimus
Procedure: BMT
Procedure: Apheresis
Procedure: Total Body Irradiation
Procedure: GCSF Injections
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Attain phenotypic correction of the disease.

Secondary Outcome Measures:
  • Obtain engraftment without development of graft vs host disease, establish stable mixed chimerism, improve radity of immune reconstitution, determine days to neutrophil recovery, measure incidence of CMV reactivation, measure transfusion require...

Estimated Enrollment: 100
Study Start Date: January 2007
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Busulfan
    Drug: Campath-1 H
    Drug: Sirolimus
    Procedure: BMT
    Procedure: Apheresis
    Procedure: Total Body Irradiation
    Procedure: GCSF Injections
Detailed Description:

Congenital immunodeficiencies - including chronic granulomatous disease, leukocyte adhesion deficiency and others - comprise a group of disorders in which the immune system fails to develop normally due to a genetic defect. As a result, affected patients suffer from recurrent infections and have a significantly shortened life expectancy. The current management of these patients is limited to close surveillance for infections, administration of prophylactic antimicrobials, and rapid and aggressive treatment of suspected and documented infections with broad-spectrum antibiotics. Although often effective, these treatments can require long hospitalizations, impacting on the overall quality of life significantly, and lead to significant morbidity, such as renal failure and deafness.

Currently, the only available cure for these disorders is bone marrow transplantation, which most commonly uses an HLA-matched related sibling as the donor (Allogeneic Stem Cell Transplantation). However, as only 30% of patients in the general population have an HLA- matched related sibling, allogeneic related transplantation is often not an option, resulting in the need for matched unrelated donor transplantation. The National Marrow Donor Program serves as both a national registry of volunteers who are willing to donate progenitor cells to eligible recipients as well as a repository of cord blood products. Despite continued improvement in the use of transplantation schemas including the development of nonmyeloablative regimens there remain significant morbidity and mortality associated with transplantation, in particular, graft versus host disease (GvHD).

GvHD is a result of the graft recognizing host antigens as foreign, typically in the presence of inflammation, and results in a type of iatrogenic autoimmune disease. For patients with non-malignant diseases, the aim of the transplant is solely to replace the defective or deficient cell population. Furthermore, as a graft versus tumor effect is not required, regimens designed to establish tolerance induction and/or stable mixed chimerism may be preferable for cure in this patient population; therefore, alternate transplant strategies can and should be used to further suppress the development of any GvHD effects. To reduce the morbidity and mortality associated with transplantation, we propose to use a combination of uniquely designed conditioning regimens to achieve adequate engraftment in congenitally immunodeficient patients and subset of patients with autoinflammatory/immunodysregulatory conditions, using either alloPBSC transplantation for patients with an HLA-matched related sibling donor, or MUD transplantation for those without an appropriate HLA-matched related sibling donor. For the alloPBSC transplantation (Group 1), we propose using a novel busulfan-based, nonmyeloablative conditioning regimen combined with Campath-1-H or h-ATG, an immunosuppressive monoclonal antibody, and sirolimus, a tolerance inducing immunosuppressant used for GvHD prophylaxis. For the MUD transplantation (Group 2), we will also use a similar conditioning regimen, with a few modifications (due to the increased risk of graft rejection with HLA-matched but unrelated cells) to perform matched unrelated and cord blood transplantation in patients with immunodeficiencies. Given its novelty, this combination will be tested in a pilot trial and will be compared to historical controls.


Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00426517

Contact: Nana Kwatemaa, R.N. (301) 451-7820
Contact: Elizabeth M Kang, M.D. (301) 402-7567

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
Principal Investigator: Elizabeth M Kang, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ) Identifier: NCT00426517     History of Changes
Other Study ID Numbers: 070075, 07-I-0075
Study First Received: January 23, 2007
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
MUD Transplant
HLA Matched Transplant
Congenital Immunodeficiency
Bone Marrow Transplant

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 23, 2014