Clinical trial NCT05589896: A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
Official title: A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Cutaneous T Cell Lymphomas (CTCL)
Keywords: Leukemia
Hematologic Diseases
ALL
AML
ABL
AUL
Bone Marrow Transplant
Lymphoma
MDS
CLL
CML
Lead sponsor: Ossium Health, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Center for International Blood and Marrow Transplant Research
First posted: 2022-10-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: All patients will receive Ossium HPC, Marrow product. Study arms will be based on order of enrollment and planned conditioning regimen.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Neutrophil Engraftment
timeFrame: Day 28
measure: Serious Adverse Events
timeFrame: Day 56
measure: CTCAE Grade 3/4 Adverse Events (AEs)
timeFrame: Day 56
measure: CTCAE Grade 3/4 Adverse Events (AEs) attributed to infusion of Ossium HPC, Marrow
timeFrame: Day 28
measure: Death
timeFrame: Day 56
Secondary outcomes:
measure: Cumulative incidences of neutrophil engraftment
timeFrame: Day 28
measure: Cumulative incidences of platelet recovery
timeFrame: Day 56
measure: Cumulative incidence of disease relapses
timeFrame: Day 365
measure: Transplant-related mortality (TRM)
timeFrame: Day 100 and Day 365
measure: Cumulative incidences of acute (aGVHD) Graft Versus Host Disease
timeFrame: Day 100, Day 180, and Day 365
measure: Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease
timeFrame: Day 100, Day 180, and Day 365
measure: Incidence of clinically-significant infections
timeFrame: Day 100 and Day 365
Other outcomes:
measure: Length of Stay in Hospital
timeFrame: Day 100 and Day 365
measure: Time to provide Ossium product to the patient from product availability request
timeFrame: Day 365
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: New York
country: United States
facility: Columbia University - Herbert Irving Comprehensive Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: TriStar Bone Marrow Transplant
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital, Texas Transplant
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Center for International Blood and Marrow Transplant Research
name: Jeffery Auletta, MD
role: STUDY_CHAIR
References: