Ignite Creation Date:
2025-12-25 @ 12:04 AM
Ignite Modification Date:
2025-12-25 @ 10:03 PM
Study NCT ID:
NCT05298358
Status:
TERMINATED
Last Update Posted:
2025-02-04
First Post:
2022-03-07
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
RIC alloBMT With Post-transplant Cyclophosphamide for Refractory Systemic Sclerosis
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Study Overview
Official Title:
A Phase I Study of Reduced Intensity Conditioning Allogeneic Bone Marrow Transplant With Post-transplant Cyclophosphamide for Refractory Systemic Sclerosis
Status:
TERMINATED
Status Verified Date:
2025-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
This study was closed due to low accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase I, single arm, open label, single center pilot study to assess a reduced-intensity conditioning regimen, bone marrow transplantation with high dose cyclophosphamide (PTCy) in recipients with refractory systemic sclerosis. This study expects to enroll 15 donor/recipient pairs for a total of 30 participants.
The primary objective of this study is to assess the safety of using a reduced intensity condition (RIC) preparative regimen bone marrow transplant (BMT) with post-transplant cyclophosphamide for graft vs host disease (GVHD) prophylaxis as treatment for patients with scleroderma. Safety events are grade III-IV GVHD and treatment related mortality within 1 year.
Eligibility includes patients \>18 years who are eligible for transplantation according to the BMT Policy Manual, meet the 2013 ACR/EULAR Criteria for Systemic Sclerosis and display active diffuse cutaneous disease.
The trial also includes analyses of the effects of BMT on skeletal and cardiac muscle using systemic scleroderma serum biomarkers of CK, aldolase, and troponin as well as periodic monitoring of circulating scleroderma auto-antibody titers, autoreactive T cells, and flow cytometric signatures over the one-year study period to correlate with response.
The primary objective of this study is to assess the safety of using a reduced intensity condition (RIC) preparative regimen bone marrow transplant (BMT) with post-transplant cyclophosphamide for graft vs host disease (GVHD) prophylaxis as treatment for patients with scleroderma. Safety events are grade III-IV GVHD and treatment related mortality within 1 year.
Eligibility includes patients \>18 years who are eligible for transplantation according to the BMT Policy Manual, meet the 2013 ACR/EULAR Criteria for Systemic Sclerosis and display active diffuse cutaneous disease.
The trial also includes analyses of the effects of BMT on skeletal and cardiac muscle using systemic scleroderma serum biomarkers of CK, aldolase, and troponin as well as periodic monitoring of circulating scleroderma auto-antibody titers, autoreactive T cells, and flow cytometric signatures over the one-year study period to correlate with response.
Detailed Description:
The purpose of this study is to find out if the drug cyclophosphamide given after bone marrow transplantation is safe and effective in patients with systemic sclerosis that have not responded to other standard treatments.
Systemic sclerosis (scleroderma) is a systemic autoimmune disease associated with high morbidity and mortality, with an estimated prevalence of 50-300 per million persons/year and incidence of 2.3-22.9 per million persons/year. Currently there exists no cure for scleroderma, and medical management is entirely off-label, with no FDA approved drugs for this condition. Treatment is based on symptom management focused on the specific organ system affected such as the lung, skin, musculoskeletal, cardiac, renal, or gastrointestinal systems.
Interest in improving response rates and decreasing relapse has turned attention toward allogeneic stem cell transplantation (allo-BMT). The possibility of maintaining control of autoimmunity by means of mixed chimerism in these autoimmune diseases is quite important. These patients may not need full engraftment to have disease modification. There is still concern about the morbidity GVHD for these patients in the allogeneic setting as well as a potentially limited number of available donors. Towards this end, the study was developed with an approach to BMT using post-transplant cyclophosphamide (PTCy) that allows safe performance of allogeneic BMT from matched, mismatched, unrelated or haploidentical donors.
Given that there are responses of refractory systemic sclerosis (SSc) to immunosuppressive therapy in some form, eligible patients will be required to have experienced disease progression despite at least one course of immunosuppressive therapy. In general, this will be defined as progression of skin or lung disease despite optimal courses of therapy or failure to tolerate therapeutic doses of immunosuppressive therapy. Potential donors will be excluded if the donors report a history of autoimmunity. The rationale for this comes from the knowledge that gender, a genetically controlled factor, plays a role in the incidence of autoimmune disease.
The study regimen includes several days of chemotherapy, immunosuppressant, and a single dose of radiation followed by the bone marrow transplant. After the transplant, recipient patients will receive two doses of the intravenous (IV, through a vein) chemotherapy cyclophosphamide and two oral medications to prevent graft versus host disease and to aid in bone marrow engraftment. After a while, the anti-rejection medications are stopped.
During this time, a chimerism assay that defines how much of the blood comes from donor cells and how much of the blood comes from the recipient will be performed at four weeks, eight weeks, six months, one year after the transplant. This test will tell if the donor's transplanted cells are surviving long term in the recipient.
If a recipient participant is eligible, the study regimen will begin about 30 days before bone marrow transplantation and participation will continue for up to 1 year after transplant.
Systemic sclerosis (scleroderma) is a systemic autoimmune disease associated with high morbidity and mortality, with an estimated prevalence of 50-300 per million persons/year and incidence of 2.3-22.9 per million persons/year. Currently there exists no cure for scleroderma, and medical management is entirely off-label, with no FDA approved drugs for this condition. Treatment is based on symptom management focused on the specific organ system affected such as the lung, skin, musculoskeletal, cardiac, renal, or gastrointestinal systems.
Interest in improving response rates and decreasing relapse has turned attention toward allogeneic stem cell transplantation (allo-BMT). The possibility of maintaining control of autoimmunity by means of mixed chimerism in these autoimmune diseases is quite important. These patients may not need full engraftment to have disease modification. There is still concern about the morbidity GVHD for these patients in the allogeneic setting as well as a potentially limited number of available donors. Towards this end, the study was developed with an approach to BMT using post-transplant cyclophosphamide (PTCy) that allows safe performance of allogeneic BMT from matched, mismatched, unrelated or haploidentical donors.
Given that there are responses of refractory systemic sclerosis (SSc) to immunosuppressive therapy in some form, eligible patients will be required to have experienced disease progression despite at least one course of immunosuppressive therapy. In general, this will be defined as progression of skin or lung disease despite optimal courses of therapy or failure to tolerate therapeutic doses of immunosuppressive therapy. Potential donors will be excluded if the donors report a history of autoimmunity. The rationale for this comes from the knowledge that gender, a genetically controlled factor, plays a role in the incidence of autoimmune disease.
The study regimen includes several days of chemotherapy, immunosuppressant, and a single dose of radiation followed by the bone marrow transplant. After the transplant, recipient patients will receive two doses of the intravenous (IV, through a vein) chemotherapy cyclophosphamide and two oral medications to prevent graft versus host disease and to aid in bone marrow engraftment. After a while, the anti-rejection medications are stopped.
During this time, a chimerism assay that defines how much of the blood comes from donor cells and how much of the blood comes from the recipient will be performed at four weeks, eight weeks, six months, one year after the transplant. This test will tell if the donor's transplanted cells are surviving long term in the recipient.
If a recipient participant is eligible, the study regimen will begin about 30 days before bone marrow transplantation and participation will continue for up to 1 year after transplant.
Study Oversight
Has Oversight DMC:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| IRB00292605 | OTHER | JHU IRB | View |