High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease
NCT ID: NCT02629120
Last Updated: 2025-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
45 participants
INTERVENTIONAL
2015-12-17
2028-12-30
Brief Summary
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Detailed Description
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Alemtuzumab, targeted busulfan, and TBI, with a 10/10 related or MUD donor graft or a 9/10 single HLA mismatch graft followed by post-transplant cyclophosphamide.
Primary Objectives:
To determine engraftment rates with the use of high cell doses, without increasing the risk of GvHD by using post-transplant cyclophosphamide and sirolimus in conjunction with a busulfan based conditioning regimen. We will compare the incidence of graft rejection/failure and GvHD to the incidence obtained from Protocol 07-I-0075.
Secondary Objectives:
To measure the engraftment rate and the engraftment kinetics using such a regimen.
To assess the level and kinetics of immune reconstitution (via chimerism) when using post- transplant cyclophosphamide.
To further elucidate the factors involved in the development of GvHD and graft rejection/failure.
To evaluate the risk of viral infections in the setting of Alemtuzumab (Campath-1H) and post-transplant cyclophosphamide.
Primary Endpoint:
Reduced incidence of graft failure or rejection (as defined by \>20% engraftment by oxidase- positive neutrophils in at least 95% of participants by Day 100, 6 months, and 1 year post BMT) will be assessed as event-free survival (EFS). Graft failure will result in disease recurrence. This will be assessed in a composite form along with GvHD (see Biostatistical Considerations section 17).
Secondary Endpoints:
Same or reduced rate of grade 3-4 aGvHD of \<20% .
Establish stable mixed chimerism.
Improve rapidity of immune reconstitution.
Overall survival.
Tertiary Endpoints:
Evaluation of inflammatory markers as risk factors for
engraftment syndrome
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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1
There is only one treatment arm for this study
Alemtuzumab
Transplant Conditioning Drug: Monoclonal antibody that targets recipient and donor T-cells to prevent graft verses host disease. Not an IND. This is a well studied drug, and is not under an IND.
Busulfan
Transplant Conditioning Drug: Chemotherapy to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow. This is a well studied drug, and is not under an IND.
Sirolimus
Immunosuppressant to prevent donor peripheral blood stem cell rejection and graft versus host disease. This is a well studied drug, and is not under an IND.
Cyclophosphamide
Post transplant cyclophosphamide given to prevent graft verses host disease. This is a well studied drug, and is not under an IND.
Total Body Irradiation
Transplant Conditioning Total Body Radiation (300cGy in 2 fractionated doses), given only to patient receiving matched unrelated donor cells, to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow.
Peripheral blood stem cells
Donor Peripheral blood stem cells, either matched unrelated donor or matched related relative to replace the patient's immune cells with functional immune cells. The peripheral blood stem cells are not regulated by the FDA.
Interventions
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Alemtuzumab
Transplant Conditioning Drug: Monoclonal antibody that targets recipient and donor T-cells to prevent graft verses host disease. Not an IND. This is a well studied drug, and is not under an IND.
Busulfan
Transplant Conditioning Drug: Chemotherapy to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow. This is a well studied drug, and is not under an IND.
Sirolimus
Immunosuppressant to prevent donor peripheral blood stem cell rejection and graft versus host disease. This is a well studied drug, and is not under an IND.
Cyclophosphamide
Post transplant cyclophosphamide given to prevent graft verses host disease. This is a well studied drug, and is not under an IND.
Total Body Irradiation
Transplant Conditioning Total Body Radiation (300cGy in 2 fractionated doses), given only to patient receiving matched unrelated donor cells, to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow.
Peripheral blood stem cells
Donor Peripheral blood stem cells, either matched unrelated donor or matched related relative to replace the patient's immune cells with functional immune cells. The peripheral blood stem cells are not regulated by the FDA.
Eligibility Criteria
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Inclusion Criteria
* 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
* When discharged from the hospital 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
* 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.
--NOTE: Alemtuzumab (Campath-1H) (intravenous \[IV\] formulation) is no longer distributed commercially. In order to receive product, the physician must contact the program for the patient. If the patient is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore no transplant will occur on this protocol.
* Patients with a CRP greater than 100 mg/L within 30 days of anticipated transplant.
* If the underlying inflammation is controlled for one month with repeat CRP testing showing a level of less than 100 on at least two separate testings, the patient will be reconsidered for transplant. If during this time period a CRP of greater than 100 is measured, then the patient would no longer be eligible for transplant.
4 Years
65 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Elizabeth M Kang, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Institute of Allergy and Infectious Diseases (NIAID)
Locations
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National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Countries
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References
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Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, Schey S, Mahendra P, Morgan GJ, Hale G, Waldmann H, de Elvira MC, Williams CD, Devereux S, Linch DC, Goldstone AH, Mackinnon S. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000 Oct 1;96(7):2419-25.
Kang EM, Hsieh MM, Metzger M, Krouse A, Donahue RE, Sadelain M, Tisdale JF. Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model. Exp Hematol. 2006 Feb;34(2):132-9. doi: 10.1016/j.exphem.2005.10.010.
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. doi: 10.1056/NEJM200103223441203.
Related Links
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NIH Clinical Center Detailed Web Page
Other Identifiers
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16-I-0032
Identifier Type: -
Identifier Source: secondary_id
160032
Identifier Type: -
Identifier Source: org_study_id