High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease

  • End date
    Dec 31, 2025
  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 15 September 2021


Chronic granulomatous disease (CGD) affects white blood cell function. Currently, the only curative treatment is bone marrow transplant to replace the abnormal stem cells with new ones (donor cells) capable of making a normal immune system. Transplant problems include graft versus host disease (GvHD) and graft rejection. With GvHD, donor cells attack the recipient s normal tissue. Researchers want to use preparation drugs and a high cell dose to increase graft success. They want to use 2 immunosuppressive drugs (cyclophosphamide and sirolimus) to lessen the risk of GvHD.


Chronic Granulomatous Disease (CGD) is an inherited disorder resulting from a failure to produce nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, necessary for protection against a number of infectious organisms. Patients are subject to recurrent infections and inflammatory complications. The current management of these participants 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. CGD patients have auto

inflammation that may manifest as inflammatory bowel disease, hypoxic lung inflammation, and/or liver nodular regenerative hyperplasia with venopathy as examples.

Currently, the only available cure for these disorders is bone marrow transplantation, which most commonly uses a human leukocyte antigen (HLA)-matched related sibling as the donor (allogeneic stem sell transplantation). However, as only 30% of participants 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 (MUD) transplantation. The National Marrow Donor Program (NMDP) 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) and graft rejection. CGD with severe autoinflammation manifested as C-reactive protein (CRP) >100 appear to be at a significantly increased risk of severe engraftment syndrome and/or GvHD, based on our results to date and will be therefore be excluded from this protocol.

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 participants 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 participant population; therefore, alternate transplant strategies can and should be used to further suppress the development of any GvHD effects.

In a prior protocol we observed low rates of GvHD, using a nonmyeloablative conditioning regimen but had significant rates of graft failure and/or loss. To improve upon our results we therefore propose to increase the target cell dose to be infused and use post transplant cyclophosphamide to mitigate the increased risk of GvHD.

For the patients with an HLA matched sibling donor (Group 1-Sibling Related) we propose using a busulfan-based, nonmyeloablative conditioning regimen combined with Alemtuzumab (Campath-1H, Campath ) an immunosuppressive monoclonal antibody currently approved by the U.S. Food and Drug Administration (FDA) as a single treatment for patients with B-cell chronic lymphocytic leukemia; however, for this protocol we are using it for its mechanism of action as an immunosuppressive agent. For GvHD prophylaxis we will use post-transplant cyclophosphamide (Cytoxan ) and sirolimus (Rapamune ).

For patients with only a MUD (Group 2-MUD) we will use a similar conditioning regimen, with a few modifications including the addition of total body irradiation (TBI) to enhance immune suppression (but with lower dose of busulfan),due to the increased risk of graft rejection with HLA-matched but unrelated cells, along with the posttransplant cyclophosphamide. We will compare the results obtained here to our previous clinical trial which did not use post transplant Cytoxan and where the cell dose infused was lower than the targeted dose of 10 million CD34+ hematopoietic stem cells/kg body weight in this study, but did use the same conditioning regimen.

Condition X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, X-Linked Chronic Granulomatious Disease, Chronic Granulomatous Disease Transplant
Treatment cyclophosphamide, busulfan, Total body irradiation, Sirolimus, Campath, allogeneic peripheral blood allograft infusion, Peripheral Blood Stem Cells, Busulfan IV, Alentuzumab (Campath)
Clinical Study IdentifierNCT02629120
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on15 September 2021


Yes No Not Sure

Inclusion Criteria

Must have confirmed Chronic Granulomatous Disease
Must have sufficient complications from underlying disease to warrant undergoing transplantation (either a history of or ongoing inflammation/CGD related autoimmunity OR a CGD related infection while on prophylaxis) OR or have a Quartile 1 and/or 2 residual oxidase production level
Ages 4 years - 65 years
HLA-matched family donor graft or an HLA matched unrelated peripheral blood stem cell (PBSC) graft (10/10 or 9/10 mismatch) 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 from one month prior to, and throughout, study participation, and for 3 months post-study. Acceptable forms of contraception are
Contraceptive pills or patch, Norplant , Depo-Provera , or other FDA-approved contraceptive method
Male partner has previously undergone a vasectomy
Male participants will be advised to consistently use contraception throughout study participation and for 3 months post-transplant

Exclusion Criteria

Eastern Cooperative Oncology Group (ECOG) or equivalent performance status greater than or equal to 3 (See Supportive Care guidelines, available at <http://intranet.cc.nih.gov/bmt/clinicalcare>)
Left ventricular ejection fraction < 40%
Transaminases > 5x upper limit of normal based on the participant s clinical situation and at the discretion of the investigator
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
Major anticipated illness or organ failure incompatible with survival from AlloPBSC transplant
Pregnant or lactating
HIV positive
Uncontrolled seizure disorder
Individuals 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
Any condition or circumstance which the PI feels would create difficulty in maintaining compliance with the requirements of this protocol
Individuals 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
Patients with a CRP greater than 100 mg/L within 30 days of anticipated transplant
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note