Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD)

Inclusion Criteria:

• Age ≥18 years

• Karnofsky score ≥70%

• No evidence of progressive bacterial, viral, or fungal infection

• Creatinine clearance >50 mL/min/1.72m2

• ALT and AST <3 x the upper limit of normal

• Total bilirubin <2 x the upper limit of normal (except for Gilbert's syndrome)

• Alkaline phosphatase ≤250 IU/L

• Left Ventricular Ejection Fraction (LVEF) >45%

• Adjusted Carbon Monoxide Diffusing Capacity (DLCO) >50%

• Negative HIV serology

• Negative pregnancy test: Confirmation per negative serum β-human chorionicgonadotropin (β-hCG)

• Willing to comply with all study procedures and be available for the duration of thestudy.

Exclusion Criteria:

• Pregnant or nursing females or women of reproductive capability who are unwilling tocompletely abstain from heterosexual sex or practice 2 effective methods ofcontraception from start of conditioning through 90 days after the last dose ofstudy drug. A woman of reproductive capability is one who has not undergone ahysterectomy (removal of the womb), has not had both ovaries removed, or has notbeen post-menopausal (stopped menstrual periods) for more than 24 months in a row.

• Male subjects who refuse to practice effective barrier contraception from the startof conditioning through a minimum of 90 days after the last dose of study drug, orcompletely abstain from heterosexual intercourse. This must be done even if they aresurgically sterilized (i.e., post-vasectomy).

• Inability to provide informed consent.

• Patient had myocardial infarction within 6 months prior to enrollment or has NewYork Heart Association (NYHA) Class III or IV heart failure (see Appendix D),uncontrolled angina, severe uncontrolled ventricular arrhythmias, orelectrocardiographic evidence of acute ischemia or active conduction systemabnormalities. Prior to study entry, any ECG abnormality at screening must bedocumented by the investigator as not medically relevant.

• Known allergies to any of the components of the investigational treatment regimen.

• Serious medical or psychiatric illness likely to interfere with participation inthis clinical study.

• Diagnosed or treated for another malignancy within 3 years of enrollment, with theexception of complete resection of basal cell carcinoma or squamous cell carcinoma,an in-situ malignancy, or low-risk prostate cancer after curative therapy.

• Participation in clinical trials with other investigational agents not included inthis trial, within 14 days of the start of this trial and throughout the duration ofthis trial.

• Prisoners

• Pregnant women