A Phase I Study of reduced intensity conditioning allogeneic bone marrow transplant with post-transplant cyclophosphamide for Refractory Systemic Sclerosis
Details
Status
Open: Currently recruiting participants.
Closed: Recruitment either has not started or has paused or completed.
Study Type
Interventional (clinical trials): Test treatments.
Observational: Conduct surveys and interviews, study medical records and otherwise observe people or groups over time.
Interventional
Study Phase
Each study phase tests different aspects of the medication or treatment:
- Phase I: safety and dosing
- Phase II: effectiveness and side effects
- Phase III: efficacy compared to standard treatments
- Phase IV: long-term safety after approval for use
Unspecified
Location(s)
Johns Hopkins study sites. Additional study locations may be found on ClinicalTrials.gov.
The Johns Hopkins Hospital
1800 Orleans St Baltimore, MD 21287
Contact Us
(410) 955-8964Brief Summary
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 an autoimmune disease like scleroderma is quite important. These patients may not need full engraftment to have disease modification that reduces symptoms of disease. However, there is still concern about serious toxicity from GVHD for these patients in the allogeneic setting as well as a potentially limited number of available donors. Towards this end, this 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.
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 (chimerism) 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.