Ignite Creation Date:
2024-05-06 @ 8:06 PM
Last Modification Date:
2024-10-26 @ 3:20 PM
Study NCT ID:
NCT06253507
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2024-07-01
First Post:
2024-02-09
Brief Title:
pCCLCHIM-p47 Lentiviral Vector Transduced CD34 Plus Cells in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease AR-CGD
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Non-Randomized Open-Label Study of pCCLCHIM-p47 Lentiviral Vector Transduced CD34 Cells in Patients With p47 Autosomal Recessive Chronic Granulomatous Disease AR-CGD
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-10-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Chronic granulomatous disease CGD is a genetic disorder People with CGD are missing a gene that affects their white blood cells White cells are part of the immune system and people with GCD are vulnerable to many infections Researchers want to test a new treatment to replace the missing gene that may be safer than the current treatment for CGD
Objective
To test a new type of gene therapy in people with CGD
Eligibility
People aged 3 years or older with CGD
Design
Participants will undergo apheresis Blood will be collected through a tube attached to a needle inserted in a vein the blood will run through a machine that separates certain cells stem cells the remaining blood will be returned to the body through a second needle The participant s stem cells will be modified in a laboratory to add the gene they are missing
Participants will stay in the hospital for about 40 days
For the first 10 days they will undergo many exams including imaging scans and tests of their heart and lung function They will receive drugs to prepare their bodies for the gene therapy They will receive a central line A hollow tube will be inserted into a vein in the chest with a port opening above the skin This port will be used to draw blood and administer drugs without the need for new needle sticks
For the gene therapy each participant s own modified stem cells will be put into their body through the port
Participants will have 8 follow-up visits over 3 years
Chronic granulomatous disease CGD is a genetic disorder People with CGD are missing a gene that affects their white blood cells White cells are part of the immune system and people with GCD are vulnerable to many infections Researchers want to test a new treatment to replace the missing gene that may be safer than the current treatment for CGD
Objective
To test a new type of gene therapy in people with CGD
Eligibility
People aged 3 years or older with CGD
Design
Participants will undergo apheresis Blood will be collected through a tube attached to a needle inserted in a vein the blood will run through a machine that separates certain cells stem cells the remaining blood will be returned to the body through a second needle The participant s stem cells will be modified in a laboratory to add the gene they are missing
Participants will stay in the hospital for about 40 days
For the first 10 days they will undergo many exams including imaging scans and tests of their heart and lung function They will receive drugs to prepare their bodies for the gene therapy They will receive a central line A hollow tube will be inserted into a vein in the chest with a port opening above the skin This port will be used to draw blood and administer drugs without the need for new needle sticks
For the gene therapy each participant s own modified stem cells will be put into their body through the port
Participants will have 8 follow-up visits over 3 years
Detailed Description:
Study Description
This is a phase III non-randomized open-label study of a single infusion of autologous CD34 cells transduced ex vivo with pCCLCHIM-p47 in 5 patients with p47-AR CGD conditioned with high dose busulfan
Objectives
Primary Objectives
To evaluate the efficacy of pCCLCHIM-p47 transduced autologous CD34 cells treatment in p47 AR-CGD patients as measured by engraftment of genetically modified cells at 6 months
Secondary Objectives
Safety
Long term engraftment assessments at 1 year 2 years and 3 years
Event Free Survival
Clinical Efficacy and Health Assessment
Exploratory Objectives
Assessment of biomarker utility
Evaluation of the human microbiome during pCCLCHIM-p47 gene therapy
Patient reported assessment of efficacy QOL
Endpoints
Primary Endpoint of this study will be engraftment of genetically modified cells as defined by presence of 10 oxidase positive cells at 6 months
Secondary Endpoints will consist of
Safety assessed by recording of the incidence of adverse events
Record clinical adverse events and clinically significant laboratory abnormalities
Evaluate overall incidence of adverse events for the study as a whole
Monitor the incidence of serious adverse events
Measure overall survival at 3 years post-transplant
Assessment of vector safety by vector insertion site analysis VISA and replication competent lentivector RCL testing
Long term multilineage engraftment as measured by
Expression of p47 phox in neutrophils at 6 12 18 24 and 36 months
Hematological reconstitution by 90 days post treatment absolute neutrophil count 500 cellsmicroliter on three consecutive samples over at least ten days
NADPH Oxidase activity in monocytes by dihydrorhodamine DHR flow cytometry at 6 12 18 24 and 36 months
Percentage of gene modified CD34 hemopoietic cells in BM at 6 12 18 24 30 and 36 months as assessed by vector copy number VCN qPCR
VCN in cell lineages present in PB cells at months 1 3 6 9 12 18 24 and 36
Event free Survival
Resolution of either underlying inflammation andor infection related to P47 deficiency without recurrence for 3 years
Rate of severe as defined by CTCAE v 50 - grade 3 to 5 CGD related infections after withdrawal of antimicrobial prophylaxis in time periods 6-12 and 6-36 months post treatment
Assessment of clinical efficacy and health by
The nutritional status height weight serum albumin at 36 months
Growth and development of pediatric subjects at 36 months
Frequency of severe infections days requiring IV antibiotics andor hospitalization for treatment at 36 months
Presence of inflammatory complications days requiring hospitalizations at 36 months
Tertiary Endpoints
Utility of Biomarker assessment
Stool collection for microbiome analysis optional
Patient Quality of life questionnaire collection
This is a phase III non-randomized open-label study of a single infusion of autologous CD34 cells transduced ex vivo with pCCLCHIM-p47 in 5 patients with p47-AR CGD conditioned with high dose busulfan
Objectives
Primary Objectives
To evaluate the efficacy of pCCLCHIM-p47 transduced autologous CD34 cells treatment in p47 AR-CGD patients as measured by engraftment of genetically modified cells at 6 months
Secondary Objectives
Safety
Long term engraftment assessments at 1 year 2 years and 3 years
Event Free Survival
Clinical Efficacy and Health Assessment
Exploratory Objectives
Assessment of biomarker utility
Evaluation of the human microbiome during pCCLCHIM-p47 gene therapy
Patient reported assessment of efficacy QOL
Endpoints
Primary Endpoint of this study will be engraftment of genetically modified cells as defined by presence of 10 oxidase positive cells at 6 months
Secondary Endpoints will consist of
Safety assessed by recording of the incidence of adverse events
Record clinical adverse events and clinically significant laboratory abnormalities
Evaluate overall incidence of adverse events for the study as a whole
Monitor the incidence of serious adverse events
Measure overall survival at 3 years post-transplant
Assessment of vector safety by vector insertion site analysis VISA and replication competent lentivector RCL testing
Long term multilineage engraftment as measured by
Expression of p47 phox in neutrophils at 6 12 18 24 and 36 months
Hematological reconstitution by 90 days post treatment absolute neutrophil count 500 cellsmicroliter on three consecutive samples over at least ten days
NADPH Oxidase activity in monocytes by dihydrorhodamine DHR flow cytometry at 6 12 18 24 and 36 months
Percentage of gene modified CD34 hemopoietic cells in BM at 6 12 18 24 30 and 36 months as assessed by vector copy number VCN qPCR
VCN in cell lineages present in PB cells at months 1 3 6 9 12 18 24 and 36
Event free Survival
Resolution of either underlying inflammation andor infection related to P47 deficiency without recurrence for 3 years
Rate of severe as defined by CTCAE v 50 - grade 3 to 5 CGD related infections after withdrawal of antimicrobial prophylaxis in time periods 6-12 and 6-36 months post treatment
Assessment of clinical efficacy and health by
The nutritional status height weight serum albumin at 36 months
Growth and development of pediatric subjects at 36 months
Frequency of severe infections days requiring IV antibiotics andor hospitalization for treatment at 36 months
Presence of inflammatory complications days requiring hospitalizations at 36 months
Tertiary Endpoints
Utility of Biomarker assessment
Stool collection for microbiome analysis optional
Patient Quality of life questionnaire collection
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001562-I | None | None | None |