High Dose Ruxolitinib and Allogeneic Stem Cell Transplantation in Myelofibrosis Patients With Splenomegaly

Inclusion Criteria:

1. Participants 18 years to less than or equal to 75 years.

2. Able to provide written consent.

3. Primary or secondary Myelofibrosis (may have received Jak inhibitors includingruxolitinib)

4. Enlarged spleen by palpation or imaging. For the purpose of this study, splenomegalyis defined as any clinically palpable spleen or spleen larger than 12 cms onimaging.

5. Has a fully matched (8/8:HLA A, B, C, DRB1) related or matched unrelated donor.

6. Adequate renal function, including: a. Serum creatinine </= 1.5 mg/dL or estimated Glomerular Filtration Rate (eGFRusing the CKI-EPI equation) >/= 40 ml/min/1.73 m2.

7. Adequate liver function, including:

8. ALT/AST </= 3 x ULN

9. Direct bilirubin </= 1mg/dL

10. No history of liver cirrhosis. No ascites.

11. Female participants of childbearing potential must have negative results for a serumpregnancy test. Female participants must agree to not breastfeed during the studyand for 3 months post-completion of the study therapy.

12. Subjects who are of childbearing potential, sexually active, and at risk ofpregnancy must agree to use a highly effective method of contraception for theduration of the active treatment and at least 3 months post-completion of the studytherapy. Highly effective methods of contraception include the following:

13. Hormonal contraception (i.e., birth control pills, injection, implant,transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation orhysterectomy, Subject/Partner post vasectomy, Implantable or injectablecontraceptives, and condoms plus spermicide. Not engaging in sexual activityfor the total duration of the trial and the drug washout period is anacceptable practice; however periodic abstinence, the rhythm method, and thewithdrawal method are not acceptable methods of birth control. Should a womanbecome pregnant or suspect she is pregnant while she or her partner isparticipating in this study, she should inform her treating physicianimmediately.

14. Men treated or enrolled on this protocol must also agree to use adequatecontraception prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able tohave children must use effective birth control while on the study. If the maleparticipant fathers a child or suspects that he has fathered a child while onthe study, he must immediately notify his doctor.

Exclusion Criteria:

1. Positive beta HCG in females of child-bearing potential defined as notpostmenopausal for 24 months or no previous surgical sterilization or lactatingfemales.

2. Ejection fraction <40%

3. Corrected DLCO < 50%

4. Evidence of other clinically significant uncontrolled condition(s) including, butnot limited to:

5. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)

6. Active hepatitis B virus (HBV), hepatitis C (HCV), HIV or TB infection orrequiring treatment for the same.

7. Thrombosis including MI, Stroke, PE, DVT in the past 6 months

Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.