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

Phase 1
Active, not recruiting
Conditions
Chronic Granulomatous Disease Transplant
Interventions
Radiation: Total Body Irradiation
Biological: Peripheral blood stem cells
Registration Number
NCT02629120
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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.

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Detailed Description

Study Description:

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

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
45
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1CyclophosphamideThere is only one treatment arm for this study
1AlemtuzumabThere is only one treatment arm for this study
1Total Body IrradiationThere is only one treatment arm for this study
1Peripheral blood stem cellsThere is only one treatment arm for this study
1BusulfanThere is only one treatment arm for this study
1SirolimusThere is only one treatment arm for this study
Primary Outcome Measures
NameTimeMethod
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...5 years

This study is still recruiting patients.

Secondary Outcome Measures
NameTimeMethod
To measure the engraftment rate and the engraftment kinetics using such a regimen5 years

This study is still recruiting patients

To assess the level and kinetics of immune reconstitution (via chimerism) when using post- transplant cyclophosphamide5 years

This study is still recruiting patients

To further elucidate the factors involved in the development of GvHD and graft rejection/failure5 years

This study is still recruiting patients

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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