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Chronic Granulomatous DiseaseEarly Phase 1NCT03910452

Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

A Early Phase 1 study testing Busulfan, Alemtuzumab and Cyclophosphamide in people with Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Background: CGD causes infections and inflammation. The only cure currently is a bone marrow transplant. Most often a perfectly matched bone marrow donor is used. Researchers want to see if they can lower the risks of using a mismatched donor. Read more about this study

Who is it for?
Ages 4 to 65 years
Conditions the study is for
Chronic Granulomatous Disease
What is being tested?
Busulfan, Alemtuzumab and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
28 Oct 2019to 15 Jun 2034
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Must have sufficient complications from underlying disease to warrant undergoing transplantation. (History of one or more life threatening infections and/or an ongoing infection not responsive to current medical therapy and/or ongoing inflammation along with an oxidase level within quartile 1 or 2.
  • Patients will be reviewed at a multidisciplinary meeting for assessment of the risk/benefit ratio of transplant for the patient to determine suitability for this high risk treatment. This multidisciplinary meeting is a combined NCI/NIAID bimonthly meeting comprised of investigators from multiple branches of the NC and NIAID to review patients with immunodeficiencies being considered for various transplant protocols.
  • Patients who are deemed to have colitis in the severe category (severe colitis) as defined below in the Subject Exclusion Criteria, who are at high risk for GvHD, will be included in enrollment to the protocol after 10 patients have completed the protocol regimen successfully. Patients among the first 10 may have colitis that is not deemed in the severe category. The success of the regimen will be determined as engraftment with a maximum GvHD of grade 2 (See the exclusion criteria for patients with severe colitis).
  • Patients who are 4 65 years of age.
  • HLA mismatched related (more than 1 mismatch) donor graft available.
  • Ability to comprehend and willingness to sign the informed consent or have a parent/guardian consent if the donor is a minor; assent being obtained from minors as appropriate.
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  • 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 with NIH Form-200 NIH Durable Power of Attorney for Health Care Decision Making."
  • Where appropriate, subjects must agree to use contraception for 3 months post-transplant.
  • NOTE: Alemtuzumab (IV formulation) is no longer distributed commercially. In order to receive product, the physician must contact the program for the patient. If the subject is not willing to consent to submit their info (address, date of birth and gender) to the program such that we can obtain the drug, then we cannot proceed with conditioning therefore no transplant will occur on this protocol.
  • Participation of Women:
  • Contraception: The effects of the combination of conditioning medications (alemtuzumab, busulfan, cyclophosphamide and mycophenolate mofetil) and total body irradiation on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post transplant. Females of childbearing-age must have a negative pregnancy test result prior to receiving any chemotherapy or conditioning agents. During the course of the study, if a woman becomes pregnant or suspects she is pregnant, she should inform the study staff and her primary care physician immediately.
  • Participation of Children:
  • Children greater than or equal to 4 years of age may participate in this study.

Who cannot join

  • The subject cannot have a 9/10 or 10/10 HLA matched related or unrelated donor.
  • Eastern Cooperative Oncology Group (ECOG) or equivalent performance status greater than or equal to 3
  • Patients with inflammatory bowel disease deemed in the severe category (severe colitis), because they are at higher risk for GvHD, will be excluded from the protocol until there are 10 patients without severe colitis that have successfully completed a regimen, as determined by engraftment and acute GvHD of a maximum of grade 2. Severity of colitis will be determined in consultation with a gastroenterologist specialist. However, severe colitis will be evaluated within 4 months of transplant and defined as any of the following (where this screening may be performed on a natural history or screening protocol):
  • The consultant gastroenterologist clinically determines that the patient has severe colitis.
  • Patient adult CDAI score is in the 350-450 range and Pediatric CDAI score is greater than 30 within the month before initiation of conditioning Crohn s Disease Activity Index (CDAI) for transplant.
  • The patient has been requiring 1 mg/kg/day or more of prednisone or equivalent steroid for control of colitis within 1 month of the CDAI scoring used to determine eligibility.
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  • The patient requires continuing treatment with a biologic that consists of anti-TNF alpha (e.g. infliximab, Humira, certolizumab and others of this family), anti-interleukin 12 (e.g. Ustekinumab) or anti-integrin (e.g. Vedolizumab) for control of colitis within 2 months of the CDAI scoring used to determine eligibility.
  • If the patient had a colonoscopy within 6 months of transplant which revealed findings of a simplified endoscopic score of Crohn s Disease (SES-CD) greater than 15.
  • Left ventricular ejection fraction < 40%.
  • Transaminases > 5x upper limit of normal.
  • Psychiatric disorder or mental deficiency severe enough as to make compliance with the HSCT treatment unlikely, and/or making regulatorily and legally effective informed consent impossible. This will include adult patients that are unable to consent.
  • Major anticipated illness or organ failure incompatible with survival from AlloPBSC transplant.
  • Pregnant or lactating.
  • HIV positive.
  • Participants older than 65 are excluded. It is known from standard transplantation that these participants have a higher risk of morbidity and mortality related to transplantation. Given the investigational nature of this protocol, the risk benefit ratio is not warranted to include these participants at this time.
  • Participants who are not willing to submit their information as part of the alemtuzumab (Campath ) Distribution Program application or participants whom the Distribution Program committee has determined are not qualified to receive alemtuzumab.
  • Any condition or circumstance, which the Principal Investigator (PI) feels, would create difficulty in maintaining compliance with the requirements of this protocol.
  • Any active infectious disease, whether CGD-related or not, that is deemed to be incompatible with successful tolerance to the rigors of transplantation.
  • C-reactive protein of greater than 100 Units within 6 weeks of anticipated transplant.
  • Any history of seizures, controlled or otherwise, if unrelated to an infectious cause.
  • Any history of any neurologic disorders or family history of such, unrelated to infection.
  • Brain CT or MRI findings suggestive of neurologic disorders other than infection.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

Background:

CGD causes infections and inflammation. The only cure currently is a bone marrow transplant. Most often a perfectly matched bone marrow donor is used. Researchers want to see if they can lower the risks of using a mismatched donor.

Read more

Objectives:

To see if it is safe to use a related bone marrow donor who is only a partial match to a person with CGD. To see how well drugs given to a person before and after transplant help the body accept the transplant.

Eligibility:

People ages 4-65 with CGD for whom stem cell transplant may be a cure and who do not have a perfectly matched donor, related or unrelated.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood tests

Participants will be admitted to the hospital about 2 weeks before the transplant. They will have blood, urine, breathing, and heart tests. They may have CT and/or MRI scans. They will have a needle inserted into their hipbone to remove marrow. They will have dental, neurologic, and psychologic tests. They will have a central catheter placed: A line will be placed into a vein in their upper chest. They will get drugs, chemotherapy, and radiation to prepare for the transplant.

Participants will receive the donated cells through their catheter. The cells will be from one of their relatives.

Participants will stay in the hospital about 6 weeks after the transplant.

After they leave the hospital, participants will have to stay in the area with visits about 2 times a week for approximately 100 days post transplant. Then visits will be every 3 to 6 months for 2 years. Then visits will be once a year.

Read the detailed description

Allogeneic transplant using human leukocyte antigen (HLA) matched donors, both related and unrelated, has proven curative for patients with various immunodeficiencies, including those with ongoing infections. However, donor availability remains a limiting factor in the application of this treatment modality. For this protocol, a haploidentical donor is a related donor with more than 1 HLA antigen mismatch. The use of haploidentical related donors has in the past been fraught with a greater rate of complications related to both higher rates of graft versus host disease (GvHD) and delayed immunorecovery. Newer transplant regimens appear to have diminished these risks and improved outcomes. We propose using a reduced intensity novel conditioning regimen using alemtuzumab, targeted busulfan, and low dose total body irradiation (see schema below) followed by post-transplant cyclophosphamide for patients with chronic granulomatous disease (CGD) who do not have an HLA matched donor but whose circumstances necessitate the use of a potentially curative, albeit high-risk treatment modality. However, patients with CGD have high rates of Crohn s Disease-like inflammatory bowel disease, predominantly colitis, where uncontrolled severe IBD may increase risk of GvHD. For this reason, the first 10 patients enrolled will exclude those deemed to have intestinal inflammation in the severe category.

As part of the study design, the protocol will enroll patients sequentially.

Keywords
Haplo-identical, Allogeneic Stem Cell Transplant, Peripheral Blood Stem Cell Transplant, Graft Versus Host Disease, Non-Myeloablative Conditioning Regimen
Medical subject headings
Granulomatous Disease, Chronic, Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BusulfanDrug

    3 days of IV Busulfan. An alkylating chemotherapeutic agent determined to have broad myelosuppressive effects. On this study is being used as part of conditioning regimen for myelosuppressive properties as per package insert and standard of care.

  • AlemtuzumabDrug

    5 days of IV Alemtuzumab. A humanized monoclonal antibody directed against CD52 (which is abundantly expressed on all human lymphocytes), and causes T cell activation in vitro as well as complement-mediated lysis and antibody-dependent cellular toxicity. For this study, being used as part of the conditioning regimen per package insert and standard of practice.

  • CyclophosphamideDrug

    2 days of IV Cyclophosphamide. This is an antineoplastic, and for this study is bine used for its immunosuppressive mechanism of action per package insert and standard of care

  • SirolimusDrug

    Post Peripheral blood stem cell infusion. It is used for its immunosuppressive mechanism of action.

  • Total Body IrradiationRadiation

    2 fractionated doses on -2 day. It is used for its immunosuppressive mechanism of action. It is SOP for conditioning for transplant.

  • Allogeneic peripheral blood stem cellBiological

    IV infused donor peripheral blood stem cell. Stem cells are cells that give rise to the blood cells - red blood cells that carry oxygen, white blood cells that help the body to fight infections, and platelets that help make the blood clot. Collected and infused per the standard of operating procedures established by the Department of Transfusion Medicine.

Study groups in NCT03910452
Study groupRoleWhat they receive
1ExperimentalThis is a single arm open-label pilot study.
Receives: Drug: Busulfan; Drug: Alemtuzumab; Drug: Cyclophosphamide; Drug: Sirolimus; Radiation: Total Body Irradiation; Biological: Allogeneic peripheral blood stem cell

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Engraftment - Chimerism

    Myeloid chimerism >50% without incurring grade 3 steroid refractory or any grade 4 acute graft versus host disease or severe extensive chronic graft versus host disease post transplant.

    Measured: Day 30, 100, 6mo, 12 mo

Secondary outcomes (3)

  1. Viral immune titrels

    Viral Immune Reconstitution using viral reactivation as a marker.

    Measured: 6 mo, 1 year, 2 year, and 3 years post transplant.

  2. Overall Survival/Event-Free survival

    1. Assessment of rates of Overall Survival and Event Free Survival (event being late graft loss or recurrence of CGD phenotype).

    Measured: continuous observation/Day +14, 30, 60, 100, 6 mo, 12 mo, 18 mo, 2,3,4,5 years

  3. DHR as a marker of normal neutrophil function

    1. Myeloid immune reconstitution levels with DHR as a marker of normal neutrophil function by 1-year post transplant.

    Measured: Day 30, 100, 6 month and 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2019
  2. Study start28 Oct 2019
  3. Primary completion15 Jun 2034 (estimated)
  4. Study completion15 Jun 2034 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03910452
Sponsor's protocol ID
190080
Other IDs
19-I-0080
Status last verified
9 Sep 2026
First submitted
9 Apr 2019
Last updated
29 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Marsh RA, Kim MO, Liu C, Bellman D, Hart L, Grimley M, Kumar A, Jodele S, Myers KC, Chandra S, Leemhuis T, Mehta PA, Bleesing JJ, Davies SM, Jordan MB, Filipovich AH. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Biol Blood Marrow Transplant. 2013 Nov;19(11):1625-31. doi: 10.1016/j.bbmt.2013.09.001. Epub 2013 Sep 10.

    PubMed 24035782

  • Munchel A, Kesserwan C, Symons HJ, Luznik L, Kasamon YL, Jones RJ, Fuchs EJ. Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide. Pediatr Rep. 2011 Jun 22;3 Suppl 2(Suppl 2):e15. doi: 10.4081/pr.2011.s2.e15.

    PubMed 22053277

  • Parta M, Kelly C, Kwatemaa N, Theobald N, Hilligoss D, Qin J, Kuhns DB, Zerbe C, Holland SM, Malech H, Kang EM. Allogeneic Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: a Single-Center Prospective Trial. J Clin Immunol. 2017 Aug;37(6):548-558. doi: 10.1007/s10875-017-0422-6. Epub 2017 Jul 28.

    PubMed 28752258

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Busulfan, Alemtuzumab and Cyclophosphamide in people with Chronic Granulomatous Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Engraftment - Chimerism (time frame: Day 30, 100, 6mo, 12 mo). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03910452, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.

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