Exploring the Potential of Dual Kinase JAK 1/2 Inhibitor Ruxolitinib (INC424) With Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis

Inclusion Criteria:

- Documented diagnosis of primary myelofibrosis according to WHO criteria or post PV
myelofibrosis or post ET myelofibrosis as per IWG-MRT criteria

- Age 18-70 years

- Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria OR
Intermediate-1 risk disease with one of the following additional unfavorable features
known to impact the survival adversely

1. Red cell transfusion dependency

2. Unfavorable Karyotype

3. Platelet count <100 x 109/l

- Blasts in the PB and BM <20% prior to study enrollment

- Availability of a suitable matched related (6/6 or 5/6) or unrelated donor (10/10 or
9/10 antigen or allele matched).

- Able to give informed written consent

- ECOG Performance status of 0-2.

- Life expectancy >3 months

- Off all MF-directed therapy including investigational agents for at least 2 weeks
prior to study enrollment and recovered from all toxicities*

- Adequate organ function

- Adequate renal function - creatinine <1.5 x IULN

- Adequate hepatic function - AST/ALT <2.5 x IULN, Total Bilirubin <1.5 x IULN

- Adequate hematopoietic function - Platelet ≥50 x 109/l and ANC ≥1.0 x 109/l

- LVEF >40% (MUGA or echocardiogram) Normal per Institutional standard

- Adequate pulmonary function with DLCO >50%

- A patient who has been on stable dose of Ruxolitinib and has received
ruxolitinib ≤6 months prior to the study entry will be considered
potentially eligible for the study with the caveat that there is no
evidence of loss of response (>5cm increase in spleen size from the nadir).

Exclusion Criteria:

- Any previous JAK2 inhibitor treatment prior to study enrollment, with the exception
of Ruxolitinib

- Hypersensitivity to JAK inhibitor

- Clinical or laboratory evidence of cirrhosis

- Prior allogeneic transplant for any hematopoietic disorder

- >20% blast in the PB or BM prior to HCT or had leukemic transformation (>20% blasts
in PB or BM any time prior to HCT)

- Syngeneic donor

- Cord Blood transplant

- Active uncontrolled infection

- H/o another malignancy within 5-years of date of HCT except h/o basal cell or
squamous cell carcinoma of skin or PV or ET

- Known HIV positive

- Pregnancy at the time of BMT

- Any other concurrent illness which in investigator's opinion puts the patient at
excessive risk of treatment related toxicities

- Unable to give informed consent

- Active infection with hepatitis A,B or C virus

- Subjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to
this study