Ignite Creation Date:
2024-05-06 @ 7:49 PM
Last Modification Date:
2024-10-26 @ 3:14 PM
Study NCT ID:
NCT06145282
Status:
RECRUITING
Last Update Posted:
2024-05-24
First Post:
2023-11-22
Brief Title:
Non-myeloablative Haploidentical HCT Study for Patients With Sickle Cell Disease Including Compromised Organ Function
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Non-myeloablative Phase III Haploidentical HCT Study for Patients With Sickle Cell Disease Including Compromised Organ Function
Status:
RECRUITING
Status Verified Date:
2024-09-20
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
Sickle cell disease SCD is a genetic disorder where red blood cells that carry oxygen are stiff and become stuck in small blood vessels As a result affected patients can experience severe pain and serious organ damage SCD can be cured with a hematopoietic cell transplant HCT that is when they receive blood stem cells from a family donor But HCT can also have serious side effects especially in people with organ damage Researchers want to find ways to make HCT safer for everyone
Objective
To test a new combination of drugs briquilimab abatacept and alemtuzumab used along with radiation in people undergoing HCT for SCD
Eligibility
People aged 16 and older with SCD They must be eligible for HCT and have a family member who is a good donor match Donors must be aged 4 and older
Design
Participants with SCD will be screened They will have blood tests and tests of organs including their heart and lung function Donors will have blood drawn
Participants with SCD will have a tube inserted into a blood vessel in their chest intravenously This line will remain in place up to 2 months it will be used to draw blood and administer the donor cells and other medications
Briquilimab will be administered intravenously 1 time along with other drugs used to prepare for HCT Participants will receive abatacept 6 times from just before they receive their donor cells until 6 months after Participants will undergo radiation therapy and take other drugs that are standard for HCT Most HCT recipients remain in the hospital for about 30 days after HCT
Follow-up visits will continue for 5 years
Sickle cell disease SCD is a genetic disorder where red blood cells that carry oxygen are stiff and become stuck in small blood vessels As a result affected patients can experience severe pain and serious organ damage SCD can be cured with a hematopoietic cell transplant HCT that is when they receive blood stem cells from a family donor But HCT can also have serious side effects especially in people with organ damage Researchers want to find ways to make HCT safer for everyone
Objective
To test a new combination of drugs briquilimab abatacept and alemtuzumab used along with radiation in people undergoing HCT for SCD
Eligibility
People aged 16 and older with SCD They must be eligible for HCT and have a family member who is a good donor match Donors must be aged 4 and older
Design
Participants with SCD will be screened They will have blood tests and tests of organs including their heart and lung function Donors will have blood drawn
Participants with SCD will have a tube inserted into a blood vessel in their chest intravenously This line will remain in place up to 2 months it will be used to draw blood and administer the donor cells and other medications
Briquilimab will be administered intravenously 1 time along with other drugs used to prepare for HCT Participants will receive abatacept 6 times from just before they receive their donor cells until 6 months after Participants will undergo radiation therapy and take other drugs that are standard for HCT Most HCT recipients remain in the hospital for about 30 days after HCT
Follow-up visits will continue for 5 years
Detailed Description:
Study Description
Haploidentical hematopoietic cell transplantation offers a widely available curative option for individuals with sickle cell disease The goal is to reverse SCD while avoiding unacceptable graft rejection graft-versus-host disease infectious complications and hyperinflammatory responses We hypothesize that a moderate amount of immunosuppression will maximize efficacy while avoiding unacceptable toxicity
Objectives
Primary Objective
-Evaluate the regimen success rate where success is defined as successful engraftment persistent donor chimerism and free of acute SCD complications and absence of acute grade 3 or higher GVHD or moderate to severe chronic GVHD evaluated at 1 year posttransplant
Secondary Objectives
Event-free survival and overall survival
Incidence of recipient-type hemoglobin defined as HbS 10 when donors have HbAA and HbS 50 when donors have sickle cell trait HbAS
The proportion of patients with myeloid chimerism 95 at 1 and 2 years post-HCT
Incidence of acute and chronic GVHD
Prevalence of donor type hemoglobin at 1-year post-transplant in SCD patients who have not been transfused in the previous 3 months
Incidence of viral reactivation and disease
Incidence of autoimmune and hyperinflammatory complications
Incidence of hematologic malignancies
Transplant-related mortality
Exploratory Objective
Perform gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34 cells collected from recipients
Evaluate the impact of this non-myeloablative conditioning regimen on organs including the heart lung kidneys liver brain neurocognitive function and endocrine organs
Evaluate the impact of this non-myeloablative conditioning regimen on quality of life
Endpoints
Primary Endpoint
-The percentage of SCD patients at 1 year - 3 months posttransplant who have not experienced graft failure and who are without severe graft-versus-host disease defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD
Secondary Endpoints
Total hemoglobin and percent HbS levels
Percent donor myeloid chimerism and donor CD3 chimerism
Day of neutrophil engraftment
Day of platelet engraftment
RBC transfusion requirement
Rates of acute and chronic GVHD
Rates of viral reactivation and disease
Rates of autoimmune and hyperinflammatory complications
Transplant-related mortality
Non-transplant-related mortality
Rates of graft failure
Rates of leukemia and related disorders
Exploratory Endpoint
Completion of gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34 cells collected from recipients
Organ function and quality of life
Haploidentical hematopoietic cell transplantation offers a widely available curative option for individuals with sickle cell disease The goal is to reverse SCD while avoiding unacceptable graft rejection graft-versus-host disease infectious complications and hyperinflammatory responses We hypothesize that a moderate amount of immunosuppression will maximize efficacy while avoiding unacceptable toxicity
Objectives
Primary Objective
-Evaluate the regimen success rate where success is defined as successful engraftment persistent donor chimerism and free of acute SCD complications and absence of acute grade 3 or higher GVHD or moderate to severe chronic GVHD evaluated at 1 year posttransplant
Secondary Objectives
Event-free survival and overall survival
Incidence of recipient-type hemoglobin defined as HbS 10 when donors have HbAA and HbS 50 when donors have sickle cell trait HbAS
The proportion of patients with myeloid chimerism 95 at 1 and 2 years post-HCT
Incidence of acute and chronic GVHD
Prevalence of donor type hemoglobin at 1-year post-transplant in SCD patients who have not been transfused in the previous 3 months
Incidence of viral reactivation and disease
Incidence of autoimmune and hyperinflammatory complications
Incidence of hematologic malignancies
Transplant-related mortality
Exploratory Objective
Perform gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34 cells collected from recipients
Evaluate the impact of this non-myeloablative conditioning regimen on organs including the heart lung kidneys liver brain neurocognitive function and endocrine organs
Evaluate the impact of this non-myeloablative conditioning regimen on quality of life
Endpoints
Primary Endpoint
-The percentage of SCD patients at 1 year - 3 months posttransplant who have not experienced graft failure and who are without severe graft-versus-host disease defined as grade 3 and higher acute GVHD and moderate to severe chronic GVHD
Secondary Endpoints
Total hemoglobin and percent HbS levels
Percent donor myeloid chimerism and donor CD3 chimerism
Day of neutrophil engraftment
Day of platelet engraftment
RBC transfusion requirement
Rates of acute and chronic GVHD
Rates of viral reactivation and disease
Rates of autoimmune and hyperinflammatory complications
Transplant-related mortality
Non-transplant-related mortality
Rates of graft failure
Rates of leukemia and related disorders
Exploratory Endpoint
Completion of gene therapy research involving cell culture or genetic manipulation to produce normal or therapeutic hemoglobin on excess autologous CD34 cells collected from recipients
Organ function and quality of life
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 |
|---|---|---|---|
| 001635-H | None | None | None |