A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies

• Ossium HPC Marrow, Bone Marrow Transplant (Other): Hematopoetic Cell Transplantation
• Pre-transplant conditioning - Myeloablative (MAC) (Other), also known as Busuflex, Fludara, TBI: Regimen A or Regimen B
• Pre-transplant conditioning - Reduced Intensity (RIC) (Other), also known as Fludara, Cytoxan, Mesnex, TBI, Melphalan: Regimen C or Regimen D
• Post-transplant treatment (Other), also known as Cytoxan, Mesnex, CellCept, Filgrastim: Post-transplant treatment

Primary outcomes

• Neutrophil Engraftment [Day 28]: Neutrophil engraftment is defined as achieving an absolute neutrophil count (ANC) of greater than or equal to 500/µL for 3 consecutive measurements on 3 different days by Day 28.
• Serious Adverse Events [Day 56]: Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.
• CTCAE Grade 3/4 Adverse Events (AEs) [Day 56]: Occurrence of any event classified as grade 3/4 AE attributed to Ossium HPC, Marrow per the CTCAE v5.0 guidelines. The time of the occurrence of each event will be recorded.
• CTCAE Grade 3/4 Adverse Events (AEs) attributed to infusion of Ossium HPC, Marrow [Day 28]: Occurrence of any event classified as grade 3 or higher attributed to Ossium HPC, Marrow infusion per the CTCAE v5.0 guidelines. The time of the occurrence will be recorded.
• Death [Day 56]: The time of death will be recorded for each expired patient.

Secondary outcomes

• Cumulative incidences of neutrophil engraftment [Day 28]: Neutrophil engraftment in defined as achieving an absolute neutrophil count (ANC) of greater than or equal to 500/µL for 3 consecutive measurements on different days by Day 28.
• Cumulative incidences of platelet recovery [Day 56]: Platelet recovery is defined as platelets greater than or equal to 20,000/µL for 3 consecutive days in the absence of transfusion for 7 consecutive days by Day 56.
• Cumulative incidence of disease relapses [Day 365]: The cumulative incidence of relapse is measured from the date of transplant (Day 0) until the date of relapse or progression; patients not known to have relapsed are censored on the date they were last examined; patients who died without relapse are counted as a competing cause of failure.
• Transplant-related mortality (TRM) [Day 100 and Day 365]: TRM is defined as death without evidence of disease progression or recurrence.
• Cumulative incidences of acute (aGVHD) Graft Versus Host Disease [Day 100, Day 180, and Day 365]: aGVHD is defined as any skin, gastrointestinal or liver abnormalities fulfilling the criteria of grades II-IV or grades III-IV.
• Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease [Day 100, Day 180, and Day 365]: cGVHD is defined per National Institutes of Health (NIH) Consensus Criteria and includes organ involvement and severity, and overall global composite score (mild/moderate/severe).
• Incidence of clinically-significant infections [Day 100 and Day 365]: A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered.

Other outcomes

• Length of Stay in Hospital [Day 100 and Day 365]: Cumulative days alive and out of the hospital in the first 100 days and in the first year post-transplant.
• Time to provide Ossium product to the patient from product availability request [Day 365]: Time from preliminary search to find a donor match in the Ossium registry and the time to provide Ossium HPC, Marrow product to recipient (time from donor availability request to delivery of product to transplant center).

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Patient has the ability to provide informed consent according to the applicable regulatory and local institutional requirements
* Male or female, aged ≥18 and ≤65 years for patients receiving MAC (Regimen A or Regimen B); aged ≥18 and ≤75 years for patients receiving RIC (Regimen C or D)
* Patient must require allogeneic HCT per the discretion of the treating physician
* Patient must be high-resolution, HLA partially or fully matched (4-8/8 allele matched at HLA-A, -B, -C, DRB1) to an available Ossium HPC, Marrow product
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Diagnosed with malignant hematologic disease including:

  1. Acute leukemia \[acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute biophenotypic leukemia (ABL), or acute undifferentiated leukemia (AUL)\], MDS without fibrosis, or chronic leukemia (CLL, CML) in the first remission or beyond with ≤5% marrow blasts documented by bone marrow assessment and no circulating blasts or extra-medullary disease within 42 days prior to anticipated start of conditioning
  2. Chemosensitive non-Hodgkin's lymphomas, Hodgkin's lymphoma, or cutaneous T cell lymphomas in the first remission or beyond documented by PET/CT imaging and bone marrow assessment within 42 days prior to anticipated start of conditioning
* Karnofsky performance status score ≥70% (MAC) or ≥60% (RIC)
* HCT comorbidity index (HCT-CI) ≤5
* Adequate organ function defined as:

  1. Cardiac: LVEF at rest ≥40% (RIC) or LVEF at rest ≥45% (MAC)
  2. Pulmonary: DLCO, FEV1, FVC ≥50% predicted by pulmonary function tests (PFTs). DLCO value may be corrected for hemoglobin.
  3. Hepatic: total bilirubin ≤2.0 mg/dL, and ALT, AST, and ALP <3 x upper limit normal (ULN), unless ALT, AST, and/or ALP are disease related
  4. Renal: SCr within 1.5x normal range for age. If SCr is outside normal range for age, CrCl> 60 mL/min/1.73m2 must be obtained (measured by 24-hour urine specimen or nuclear glomerular filtration rate (GFR), or calculated GFR)

Exclusion Criteria:

* Availability of suitable graft from living donor (defined as 7/8 or 8/8 HLA-matched related or unrelated donors, haploidentical donors, or cord blood donors)
* Prior autologous or allogeneic HCT
* Pregnancy or lactation
* Ongoing treatment with an investigational drug used for disease-related treatment within 5 half-lives of the drug
* Current uncontrolled bacterial, viral or fungal infection defined as currently taking medication with evidence of progression of clinical symptoms or radiologic findings
* Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that in the investigator's opinion precludes participation