Phase I-II PTCy, Bortezomib and Sitagliptin for Prevention of GvHD Following Allogeneic HSCT

Inclusion Criteria: 1. Patients with any of the following hematologic malignancies: 1. AML in first remission (CR1) if they have intermediate- or high-risk cytogenetic and/or molecular features, or patients in second or subsequent complete remission (CR2, CR3, etc.). Complete remission is defined as presence of \<5% blasts in the bone marrow with no morphological evidence of leukemia. Patients in CR with incomplete count recovery may be included. 2. ALL with any of the following in CR1 or subsequent complete remission (CR2, CR3, etc.). Complete remission is defined as presence of \<5% blasts in the bone marrow with no morphological evidence of leukemia. Patients in CR with incomplete count recovery may be included. 3. MDS with a revised International Prognostic System Score (IPSS-R) of greater than 3 at diagnosis. Patients must have \<10% blasts in the bone marrow documented within 30 days of transplant.\* 4. Therapy-related myelodysplastic disorder (t-MDS). Patients must have \<10% blasts in the bone marrow documented within 30 days of transplant.\* 5. CMML type 1 or 2. Patients must have \<10% blasts in the bone marrow documented within 30 days of transplant.\* \*Patients with MDS, t-MDS, and CMML will be included only in the phase I portion of the study. 2. Patient age ≥ 18 years 3. KPS ≥70% 4. Patients must also be suitable to receive an RIC regimen at the discretion of the treating physician. While there are not universally accepted or validated cut-off criteria of age, performance status, or HCT-CI for suitability for RIC, RIC transplants should be considered for patients 60 years and older and for patients \<60 years who are "less fit" (e.g., KPS \<90% and/or HCT-CI ≥3 due to lower non-relapse mortality associated with RIC). 5. Patients receiving allogeneic PBSC grafts from HLA-matched (5/6 and 6/6 matches) siblings or matched unrelated donors (7/8 or 8/8 matches at HLA-A, B, C, DRB1 by high resolution typing) are included. All grafts will be unmanipulated (i.e., no T cell depleted or CD34 selected grafts). In addition, donors should meet institutional criteria for donation of PBSC, as well as the screening and eligibility criteria of the (NMDP) for unrelated donors, and the requirements of the United States Food and Drug Administration for HCT/P (21 CFR Part 1271). 6. Required baseline laboratory values within 16 days prior to admission: 1. Estimated creatinine clearance \>60 mL/min/1.72 m2 2. Serum total bilirubin ≤2 x upper limit of normal value (except for Gilbert's disease) 3. AST and ALT ≤3 x upper limit of normal value 4. ALP ≤250 IU/l 7. Required baseline values within 60 days prior to admission: 1. LVEF \>40% 2. Adjusted carbon monoxide diffusing capacity (DLCO) \>50% 8. No evidence of HIV infection (patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies) 9. Non-pregnant and non-nursing 10. Signed written informed consent (patient must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent) 11. Patients must otherwise fulfill institutional criteria for eligibility to undergo reduced-intensity allogeneic stem cell transplantation Exclusion Criteria: 1. Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice effective methods of contraception from start of conditioning through a minimum of 90 days after the last dose of study drug. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 consecutive months. 2. Male subjects who refuse to practice effective barrier contraception from the start of conditioning through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post- vasectomy). 3. Inability to provide informed consent. 4. Patient had myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant. 5. Patients with active central nervous system leukemia 6. Prior allogeneic HSCT or an autologous HSCT in past 12 months 7. Patients with diabetes mellitus requiring insulin secretagogues and/or insulin at time of enrollment 8. Patients with a history of pancreatitis 9. Patients with symptomatic cholelithiasis 10. Known hypersensitivity to any of the components of the investigational treatment regimen 11. Serious medical or psychiatric illness likely to interfere with participation in this clinical study 12. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy 13. Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial, and throughout the duration of this trial 14. Prisoners