Ruxolitinib Pre-, During- and Post-HSCT for Patients With Primary or Secondary Myelofibrosis.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has approved Ruxolitinib as a treatment option for this disease.

This is a multi-center, open-label, phase II study to assess the efficacy and tolerability of ruxolitinib patients with myelofibrosis before, during and after hematopoietic stem cell transplantation (HCT). Eligible patients will take ruxolitinib twice daily on a continuous basis, per its FDA indication before HCT. Patients may be receiving ruxolitinib for any period of time at a dose based on institutional practice prior to enrollment to the study. Prior to enrollment, patients already receiving ruxolitinib will undergo dose-reduction to a dose of 5 mg BID, one week before conditioning begins. Patients not currently receiving ruxolitinib will enroll in the study and initiate ruxolitinib at a dose of 5 mg BID one week before conditioning begins. All patients will remain on ruxolitinib 5 mg BID during conditioning and transplant. Once patients have recovered their blood counts, patients will increase the dose (cytopenias permitting) to 10 mg BID. Patients will remain on ruxolitinib for 1 year after transplant, at which point ruxolitinib will be tapered and discontinued. Dose escalation will be permitted in patients with splenomegaly or myelofibrosis related symptoms.

Ruxolitinib is a medication that blocks certain proteins called tyrosine kinases. Specifically, it blocks tyrosine kinases called JAK2. Many cancers have over active "cell signaling." What this means is that certain functions in the cancer cells never turn off and this makes them grow in an uncontrolled way. Ruxolitinib, shuts down the pathway that depends on the JAK2 tyrosine kinases. The JAK2 pathway is over active in the participant's disease, acute myeloid leukemia. The exact way ruxolitinib does this is not yet clear but it may have to do with its ability to block the JAK2 pathway since this pathway can also lead to inflammation in the body.

Ruxolitinib has also been shown to lower the rates of Graft-Versus-Host-Disease (GVHD), a complication of transplant. GVHD is a disease that occurs when the immune cells in transplanted donor tissue from your HCT attack the participant's own tissues and organs. There are two types of GVHD: acute and chronic. Acute GVHD generally occurs within 1 week to 3 months after your HCT and may affect your skin, intestines, and liver. Chronic GVHD begins later on and may affect the organs prone to acute GVHD complications, as well as the lungs, mucous membranes, or other organs.

There is also evidence that ruxolitinib is associated with reduced instances of enlarged spleen size after HCT. Enlarged spleens play a role in the engraftment rate after HCT, which is the rate at which donated tissue and your own tissue begin reproducing and growing together.

In this research study, the investigators are:

• assessing the efficacy (how well the study drug works) and tolerability of Ruxolitinib before, during, and after HCT.
• examining the rates of GVHD after HCT when ruxolitinib is administered.
• determining whether engraftment rates improve when ruxolitinib is given