Ruxolitinib With Azacitidine Maintenance for the Treatment of Patients With Acute Myeloid Leukemia Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation
brief summary
This phase I trial studies the side effects and best dose of ruxolitinib (Rux) therapy alone (monotherapy) followed by Rux plus azacitidine (AZA) maintenance therapy and to see how well it works in treating patients with acute myeloid leukemia (AML) who are undergoing reduced intensity allogeneic hematopoietic stem cell transplantation (alloHSCT). AlloHSCT provides the only chance for cure for many patients with AML. AlloHSCT is a procedure in which a person receives blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. This is often a sister or brother, but could be an unrelated donor. One of the common reasons for death after an alloHSCT is graft versus host disease (GVHD), which occurs when the transplanted cells from the donor attacks the recipient's normal cells. Ruxolitinib is in a class of medications called kinase inhibitors. It works to treat GVHD by blocking the signals of the cells that cause GVHD. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow. Giving Rux after the transplant may stop GVHD from occurring. Maintenance therapy with AZA, may help prevent or delay cancer from coming back. Giving Rux monotherapy followed by Rux plus AZA maintenance therapy may be safe, tolerable, and/or effective in treating patients with AML who are undergoing alloHSCT.
detailed description
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of Rux monotherapy (part A) and Rux plus AZA therapy (part B) following alloHSCT in AML patients.
SECONDARY OBJECTIVES:
I. To determine the feasibility of Rux plus AZA maintenance. II. To determine the effect on measurable residual disease (MRD) of Rux plus AZA maintenance.
III. To determine the impact on neutrophil engraftment of study treatment. IV. To determine the impact on platelet engraftment of study treatment. V. To determine the frequency and timing of disease relapse after alloHSCT when treated with Rux plus AZA maintenance.
VI. To determine risk of post alloHSCT acute graft versus host disease (aGVHD) when treated with Rux plus AZA maintenance.
VII. To determine risk of post alloHSCT chronic graft versus host disease (cGVHD) when treated with Rux plus AZA maintenance.
VIII. To determine post alloHSCT survival in the absence of GVHD or disease relapse when treated with Rux plus AZA maintenance.
IX. To determine the rate of post alloHSCT early infection in context of Rux plus AZA maintenance.
X. To determine overall survival after alloHSCT and treatment with Rux plus AZA maintenance.
XI. To determine the effect on quality of life (QoL) of post alloHSCT Rux plus AZA maintenance.
EXPLORATORY OBJECTIVES:
I. To evaluate the impact of pre transplant disease characteristics on treatment outcomes.
II. To determine the impact of MRD on treatment outcomes. III. To explore biomarkers predictive of patient outcomes while on treatment.
OUTLINE: This is a dose-escalation study of azacitidine in combination with fixed-dose cyclophosphamide, tacrolimus, mycophenolate mofetil, and ruxolitinib.
PART A: Patients undergo standard of care (SOC) reduced intensity conditioning (RIC) or non-myeloablative (NMA) conditioning followed by alloHSCT on day 0 and receive cyclophosphamide intravenously (IV) over 1-2 hours on days +3 and +4, tacrolimus orally (PO) or IV daily on day + 5 and tapered per institutional protocol through day +180, and mycophenolate mofetil PO or IV three times daily (TID) on days +5 to +35 in the absence of disease progression or unacceptable toxicity. Staring on day +5, patients also receive ruxolitinib PO twice daily (BID) continuously and tapered through post-treatment day 28. Treatment with ruxolitinib continues through screening of part B in the absence of disease progression or unacceptable toxicity.
official title
A Phase I Study to Evaluate the Safety of Ruxolitinib in Combination With Azacitidine Maintenance in Patients Undergoing Reduced Intensity Allogeneic Transplant for Acute Myeloid Leukemia (AML)