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

Ossium Health

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute Biphenotypic Leukemia; Acute Leukemia; Acute Undifferentiated Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia

Treatments: Other: Ossium HPC Marrow, Bone Marrow Transplant; Other: Pre-transplant conditioning - Myeloablative (MAC); Other: Pre-transplant conditioning - Reduced Intensity (RIC); Other: Post-transplant treatment

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT05589896

PRESERVE I

Details and patient eligibility

About

The goal of this clinical trial is to determine the safety and feasibility of allogeneic transplantation with bone marrow from a deceased donor in patients with acute leukemias. Patients will either receive myeloablative conditioning or reduced intensity conditioning regimen prior to the transplant. Patients will be followed for 56 days for safety endpoints and remain in follow-up for one year.

Enrollment: 12 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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 <55 years for patients receiving MAC (Regimen A or Regimen B); aged ≥18 and <70 years for patients receiving RIC (Regimen C in Cohort 2 only)

• 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 acute leukemia [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute biophenotypic leukemia (ABL), or acute undifferentiated leukemia (AUL)] in the first remission or beyond with ≤5% marrow blasts and no circulating blasts or extra-medullary disease documented by 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 ≥45% (RIC) or LVEF at rest ≥40% (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 (by Cockcroft-Gault formula))

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Cohort 1

Experimental group

Description:

Bone Marrow Transplant with Ossium HPC, Marrow Pre-transplant myeloablative conditioning treatment with: Regimen A(MAC): Busulfan and Fludarabine \[OR\] Regimen B(MAC): Fludarabine and Total Body Irradiation Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim

Treatment:

Other: Post-transplant treatment

Other: Pre-transplant conditioning - Myeloablative (MAC)

Other: Ossium HPC Marrow, Bone Marrow Transplant

Cohort 2

Experimental group

Description:

\*Open to enrollment after DSMB review of Cohort 1 safety events through Day 56\* Bone Marrow Transplant with Ossium HPC, Marrow Pre-transplant conditioning treatment with:Regimen A(MAC): Busulfan and Fludarabine \[OR\] Regimen B(MAC): Fludarabine and Total Body Irradiation \[OR\] Regimen C(RIC): Fludarabine, Cyclophosphamide, and Total Body Irradiation Post-Transplant treatment with Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, and Filgrastim

Treatment:

Other: Post-transplant treatment

Other: Pre-transplant conditioning - Reduced Intensity (RIC)

Other: Pre-transplant conditioning - Myeloablative (MAC)

Other: Ossium HPC Marrow, Bone Marrow Transplant