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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Leukemia; Acute Undifferentiated Leukemia; Acute Biphenotypic Leukemia
• Intervention / Treatment: Other: Ossium HPC Marrow, Bone Marrow Transplant; Other: Pre-transplant conditioning - Myeloablative (MAC); Other: Post-transplant treatment; Other: Pre-transplant conditioning - Reduced Intensity (RIC)

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Matthew Flores; Phone Number: (763)406-3060; Email: PRESERVE@nmdp.org
• Study Contact Backup: Name: Preethi Prasad, MSc.; Email: preethi.prasad@ossiumhealth.com

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Eric Carrasquillo
      • Principal Investigator: Taiga Nishihori, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University - Herbert Irving Comprehensive Cancer Center
      • Contact: Elizabeth Shelton, MPH
      • Principal Investigator: Markus Mapara, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • TriStar Bone Marrow Transplant
      • Principal Investigator: Jeremy Pantin, MD
      • Contact: Yesenia Romero Herazo
  • Texas
    • Austin, Texas, United States, 78745
      • Recruiting
      • St. David's South Austin Medical Center
      • Contact: Stephanie Goldin
      • Principal Investigator: Uttam Rao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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	Other: Ossium HPC Marrow, Bone Marrow Transplant; Hematopoetic Cell Transplantation; Other: Pre-transplant conditioning - Myeloablative (MAC); Regimen A or Regimen B; Other Names: Fludara; TBI; Busuflex; Other: Post-transplant treatment; Post-transplant treatment; Other Names: Filgrastim; Cytoxan; CellCept; Mesnex
Experimental: Cohort 2; *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	Other: Ossium HPC Marrow, Bone Marrow Transplant; Hematopoetic Cell Transplantation; Other: Pre-transplant conditioning - Myeloablative (MAC); Regimen A or Regimen B; Other Names: Fludara; TBI; Busuflex; Other: Post-transplant treatment; Post-transplant treatment; Other Names: Filgrastim; Cytoxan; CellCept; Mesnex; Other: Pre-transplant conditioning - Reduced Intensity (RIC); Regimen C; Other Names: Fludara; Cytoxan; TBI; Mesnex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophil Engraftment	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.	Day 28
Serious Adverse Events	Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.	Day 56
CTCAE Grade 3/4 Adverse Events (AEs)	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.	Day 56
Death	The time of death will be recorded for each expired patient.	Day 56
CTCAE Grade 3/4 Adverse Events (AEs)	Occurrence of any event classified as grade 3 or higher attributed to Ossium HPC, Marrow per the CTCAE v5.0 guidelines as defined in Section 8.5. The time of the occurrence will be recorded.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidences of neutrophil engraftment	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.	Day 28
Cumulative incidences of platelet recovery	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.	Day 56
Cumulative incidence of disease relapses	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.	Day 365
Transplant-related mortality (TRM)	TRM is defined as death without evidence of disease progression or recurrence.	Day 100 and Day 365
Cumulative incidences of acute (aGVHD) Graft Versus Host Disease	aGVHD is defined as any skin, gastrointestinal or liver abnormalities fulfilling the criteria of grades II-IV or grades III-IV.	Day 100, Day 180, and Day 365
Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease	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).	Day 100, Day 180, and Day 365
Incidence of clinically-significant infections	A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered.	Day 100 and Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay in Hospital	Cumulative days alive and out of the hospital in the first 100 days and in the first year post-transplant.	Day 100 and Day 365
Time to provide Ossium product to the patient from product availability request	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).	Day 365

Collaborators and Investigators

• Sponsor: Ossium Health, Inc.
• Collaborators: Center for International Blood and Marrow Transplant Research
• Investigators: Study Chair: Jeffery Auletta, MD, Center for International Blood and Marrow Transplant Research

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: October 18, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: AML; ALL; Leukemia; Hematologic Diseases; Bone Marrow Transplant; ABL; AUL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Leukemia, Lymphoid; Hematologic Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine; Mesna
• Other Study ID Numbers: PRESERVE I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No