This phase II trial compares cyclophosphamide, sirolimus, and ruxolitinib to cyclophosphamide, sirolimus, and mycophenolate mofetil (MMF) after allogeneic stem cell transplantation for the prevention of graft versus host disease (GVHD) in patients with acute myeloid leukemia (AML), myelodysplastic syndrome, or chronic myelomonocytic leukemia. Patients who undergo allogeneic stem cell transplantation are at risk of developing a side effect called GVHD. GVHD is when transplanted donor cells attack the cells of the recipient's body. It is standard care for patients to receive cyclophosphamide, sirolimus, and MMF after a transplant to help prevent GVHD. Cyclophosphamide is in a class of medications called alkylating agents. It may lower the body’s immune response. Sirolimus is used to keep the body from rejecting bone marrow transplants. It blocks certain white blood cells that can reject foreign tissues and organs. It also blocks a protein that is involved in cell division. Ruxolitinib may stop GVHD by blocking some of the enzymes needed, which may lead to a reduction in inflammation. MMF is a type of immunosuppressive agent used to decrease the body's immune response and may stop GVHD. Giving cyclophosphamide, sirolimus, and ruxolitinib after allogeneic stem cell transplantation may be a more effective way to prevent GVHD in patients with AML, myelodysplastic syndrome, or chronic myelomonocytic leukemia.
Additional locations may be listed on ClinicalTrials.gov for NCT06973668.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Active
Contact: Uday R. Popat
Phone: 713-745-0049
PRIMARY OBJECTIVE:
I. To compare grade 2-4 acute graft versus host disease-free survival (GFS) between the MMF and ruxolitinib arms.
SECONDARY OBJECTIVES:
I. To compare the following between treatment arms:
Ia. Grade 3-5 adverse event of this regimen as per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 criteria;
Ib. Graft versus host disease-free, relapse-free survival (GRFS);
Ic. Time to neutrophil and platelet engraftment;
Id. Incidence of acute and chronic GVHD;
Ie. Relapse incidence;
If. Non relapse mortality;
Ig. Overall survival;
Ih. Progression-free survival;
Ii. Chimerism;
Ij. Immunosuppression cessation time;
Ik. Rate of graft failure.
EXPLORATORY OBJECTIVE:
I. To conduct mechanistic studies to compare immune recovery between arms and correlate these with disease control and GVHD prophylaxis.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive standard of care (SOC) transplant conditioning with venetoclax orally (PO) once daily (QD) on days -22 to -3, busulfan intravenously (IV) over 180 minutes on days -20, -13, and -6 to -3, thiotepa IV over 4 hours on day -7, and fludarabine IV over 1 hour and cladribine IV over 2 hours on days -6 to -3 in the absence of disease progression or unacceptable toxicity. Patients then undergo SOC allogeneic stem cell transplantation on day 0. Patients then receive cyclophosphamide IV over 3 hours on days +3 and +4 and sirolimus PO QD continuously starting on day +5 and tapered around day +100 or day +180. Patients also receive MMF IV or PO three times daily (TID) on days +5 to day +60 in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive SOC transplant conditioning and undergo SOC allogeneic stem cell transplantation as described in arm A. Patients then receive cyclophosphamide IV over 3 hours on days +3 and +4 and sirolimus PO QD continuously starting on day +5 and tapered around day +100 or day +180. Patients also receive ruxolitinib PO every 12 hours on days +5 to +60 and then tapered to PO QD on days +61 to +65 in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo echocardiography (ECHO) at baseline and bone marrow aspiration, if clinically indicated, throughout the trial. Patients may also optionally undergo blood sample collection throughout the trial.
After completion of study treatment, patients are followed up at months 3, 4, 5, 6, and 12.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorUday R. Popat
