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

Phase 1

Recruiting

• Conditions: Acute Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Biphenotypic Leukemia; Acute Undifferentiated Leukemia; CLL (Chronic Lymphocytic Leukemia); Chronic Myeloid Leukemia (CML); MDS (Myelodysplastic Syndrome); Non-Hodgkin Lymphomas; Hodgkins Lymphoma
• Interventions: Other: Ossium HPC Marrow, Bone Marrow Transplant; Other: Pre-transplant conditioning - Myeloablative (MAC); Other: Pre-transplant conditioning - Reduced Intensity (RIC); Other: Post-transplant treatment

• Registration Number: NCT05589896
• Lead Sponsor: Ossium Health, Inc.

Brief Summary

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 and chronic leukemias, myelodysplastic syndrome, and certain lymphomas. 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-18
• Study First Submitted QC: 2022-10-18
• Study First Posted: 2022-10-21
• Study Start: 2024-08-16
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-27
• Primary Completion: 2026-08
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Post-transplant treatment	\*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
Cohort 1	Post-transplant treatment	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
Cohort 2	Ossium HPC Marrow, Bone Marrow Transplant	\*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
Cohort 2	Pre-transplant conditioning - Myeloablative (MAC)	\*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
Cohort 1	Pre-transplant conditioning - Myeloablative (MAC)	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
Cohort 2	Pre-transplant conditioning - Reduced Intensity (RIC)	\*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
Cohort 1	Ossium HPC Marrow, Bone Marrow Transplant	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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).

Trial Locations

Locations (9)

City of Hope; 🇺🇸 Duarte, California, United States

Henry Ford Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Methodist Hospital, Texas Transplant; 🇺🇸 San Antonio, Texas, United States

University of Utah - Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Columbia University - Herbert Irving Comprehensive Cancer Center; 🇺🇸 New York, New York, United States

TriStar Bone Marrow Transplant; 🇺🇸 Nashville, Tennessee, United States

St. David's South Austin Medical Center; 🇺🇸 Austin, Texas, United States