This phase I trial tests the safety, best dose, and effectiveness of ruxolitinib with or without abatacept in preventing graft versus host disease (GVHD) and cytokine release syndrome (CRS) after a haploidentical stem cell transplant in patients with hematologic malignancies. A stem cell is a type of cell found in the blood or bone marrow that helps form more blood cells. A stem cell transplant uses stem cells from a healthy donor to replace the diseased bone marrow in the recipient. A haploidentical stem cell transplant is a transplant that uses a donor that is half matched. GVHD, a possible side effect of stem cell transplants, occurs when some of the cells from the donor attack the tissues of the transplant recipient. CRS, another possible side effect, is a systemic inflammatory reaction caused by the release of an excessive amount of cytokines that can cause symptoms such as fever, rapid heartbeat, low blood pressure and trouble breathing. Ruxolitinib is a Janus-associated kinase (JAK) inhibitor that works by blocking the signals of the cells involved with cell growth and spread and immune response. Abatacept is used to decrease the body's immune response against the donor cells. Ruxolitinib with or without abatacept may be safe, tolerable and/or effective in preventing GVHD and CRS after a haploidentical stem cell transplant in patients with hematologic malignancies.
Additional locations may be listed on ClinicalTrials.gov for NCT06008808.
Locations matching your search criteria
United States
Missouri
Saint Louis
Siteman Cancer Center at Washington UniversityStatus: Active
Contact: Ramzi Abboud
Phone: 314-454-8304
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of the JAK inhibitor ruxolitinib with and without the CTLA-4 immunoglobulin (Ig) abatacept with haploidentical hematopoietic cell transplantation (HCT), as measured by:
Ia. Cumulative incidence of graft failure at day 35;
Ib. Cumulative incidence of grade III-IV acute GVHD by Mount Sinai Acute GVHD International Consortium (MAGIC) criteria at day 100;
Ic. The incidence and severity of CRS.
SECONDARY OBJECTIVES:
I. To assess the feasibility of treating patients undergoing haploidentical HCT with ruxolitinib with or without abatacept.
II. To determine the cumulative incidence of grades II-IV acute GVHD at day 100.
III. To determine non-relapse mortality at day 180.
EXPLORATORY OBJECTIVES:
I. To determine the cumulative incidence of relapse at 6 months and 1 year.
II. To determine overall survival at 6 months and 1 year.
III. To determine the cumulative incidence of failure of platelet engraftment at day 35.
IV. To determine GVHD relapse-free survival (GRFS) at 1 year.
V. To assess the incidence and types of infections within 1 year.
VI. To determine the cumulative incidence of grades II-IV acute GVHD at day 180.
VII. To determine the cumulative incidence of grades III-IV acute GVHD at day 180.
VIII. To determine the cumulative incidence of chronic GVHD at 1 year.
IX. To determine the incidence of IL-6 inhibitor therapy.
OUTLINE: This is a phase I dose-escalation study of ruxolitinib. Patients are assigned to 1 of 2 regimens.
REGIMEN 1: Patients undergo pre-transplant conditioning per treating physician with fludarabine, cyclophosphamide and single dose total body irradiation (TBI) or fludarabine and fractionated TBI or fludarabine and busulfan prior to transplant. Patients receive ruxolitinib orally (PO) twice daily (BID) or once daily (QD) on days -3 to 180 and may receive tapered doses BID or QD between days 181 and 293. Patients undergo haploidentical stem cell transplantation on day 0. Patients also receive tacrolimus PO or intravenously (IV) beginning on day 5 and continuing for at least 100 days prior to tapering of ruxolitinib, cyclophosphamide on days 3 and 4, and mycophenolate mofetil PO three times daily (TID) on days 5-28. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and may undergo positron emission tomography (PET)/computed tomography (CT) scan at screening and undergo collection of blood samples and bone marrow biopsy at screening and on study.
REGIMEN 2: Patients undergo pre-transplant conditioning per treating physician with fludarabine, cyclophosphamide and single dose TBI or fludarabine and fractionated TBI or fludarabine and busulfan prior to transplant. Patients receive ruxolitinib PO BID or QD on days -3 to 180 and may receive tapered doses BID or QD between days 181 and 293. Patients undergo haploidentical stem cell transplantation on day 0. Patients also receive tacrolimus PO or IV beginning on day 5 and continuing for at least 60 days prior to tapering of ruxolitinib, cyclophosphamide on days 3 and 4, and abatacept IV over 60 minutes on days 5, 14, 28 and 56. Treatment given in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA and may undergo PET/CT scan at screening and undergo collection of blood samples and bone marrow biopsy at screening and on study.
After completion of study treatment, patients are followed up every other month for 12 months then every 3 months for up to 24 months after transplantation.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorRamzi Abboud
