Propylene Glycol-Free Melphalan HCl (EVOMELA®) in Combination with Fludarabine and Total Body Irradiation Based Reduced Intensity Conditioning for Haploidentical Transplantation

Inclusion Criteria:

• Patients with a diagnosis of hematological malignancy undergoing a related donorhaploidentical HCT.*

• Patients aged ≥18 are eligible.

• Bilirubin ≤ 2 x the upper limit of normal (ULN). For patients with Gilbert'ssyndrome or suspected mild veno-occlusive disease, bilirubin ≤ 3 x ULN is permitted.

• Adequate renal function as defined by a serum creatinine clearance of > 30 mL/mincalculated by Cockcroft-Gault equation.

• Left ventricular ejection fraction ≥40%. No uncontrolled arrhythmias or New YorkHeart Association class III-IV heart failure.

• Forced expiratory volume (FEV1) or diffusion capacity for carbon monoxide (DLCO)corrected for hemoglobin ≥ 50% of predicted.

• Karnofsky performance status > 60.

• Graft source of peripheral blood (the infused cluster of differentiation 34 (CD34)+cell dose will be capped at 5 x 10^6 CD34+ cells/kg recipients actual body weight)or bone marrow (the ideal infused total nucleated cell dose (TNC) will be targetedat 4 x 10^8/kg recipient actual body weight).

• A negative pregnancy test will be required for all women of child bearing potential.Females of child bearing potential should agree to practice 2 effective methods ofcontraception, at the same time, from the time of signing the informed consent formthrough 90 days after the last dose of study drug and must also adhere to theguidelines of any treatment-specific pregnancy prevention program, if applicable, oragree to practice true abstinence when this is in line with the preferred and usuallifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation,symptothermal, postovulation methods] and withdrawal are not acceptable methods ofcontraception.). Breast-feeding is not permitted.

• Male patients, even if surgically sterilized (i.e., status post-vasectomy), mustagree to one of the following: practice effective barrier contraception during theentire study treatment period and through 90 days after the last dose of study drug,or must also adhere to the guidelines of any treatment-specific pregnancy preventionprogram, if applicable, or agree to practice true abstinence when this is in linewith the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g.,calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are notacceptable methods of contraception.)

• No evidence of uncontrolled bacterial, viral or fungal infections at the time ofenrollment.

• Transplant recipient able to give informed consent. * Patients must be humanleukocyte antigen (HLA) typed at high resolution using DNA based typing at thefollowing HLA loci: HLA-A, -B, -C and DRB1 and have available: A relatedhaploidentical bone marrow donor with two, three or four HLA-mismatches. Aunidirectional mismatch in either the graft-versus-host or host-versus-graftdirection is considered a mismatch. The donor and recipient must be HLA identicalfor at least one antigen (using high-resolution DNA-based typing) at the followinggenetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this criterion shallbe considered sufficient evidence that the donor and recipient share one HLAhaplotype, and typing of additional family members is not required.

Exclusion Criteria:

• Patient must not have a healthy, eligible and readily available HLA-identicalsibling donor or a volunteer adult unrelated donor (matched at allele-level atHLA-A, -B, -C and -DRB1).

• No serious medical or psychiatric illness that could, in the investigator's opinion,potentially interfere with the completion of treatment according to this protocol.\

• Presence of active disease in acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS): patients with active disease defined as >5% blasts in bone marrow and/orcirculating leukemic blasts in peripheral blood, patients with known active centralnervous disease involvement with leukemia/lymphoma or lymphoma patients withprogressive disease on clinical and/or radiographic assessment are not eligible forthis study.