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.
Brief Title
A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies
Central Contacts
Central Contact Role
Contact
Central Contact Phone
628-842-6562
Central Contact Email
preethi.prasad@ossiumhealth.com
Completion Date
Completion Date Type
Estimated
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)
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
* 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
Inclusion 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)
* 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)
Gender
All
Gender Based
false
Keywords
Leukemia
Hematologic Diseases
ALL
AML
ABL
AUL
Bone Marrow Transplant
Lymphoma
MDS
CLL
CML
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT05589896
Org Class
Industry
Org Full Name
Ossium Health, Inc.
Org Study Id
PRESERVE I
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Neutrophil Engraftment
Outcome Time Frame
Day 28
Outcome Description
Occurrence of any event classified as SAE. The time of occurrence of each serious adverse event will be recorded.
Outcome Measure
Serious Adverse Events
Outcome Time Frame
Day 56
Outcome Description
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.
Outcome Measure
CTCAE Grade 3/4 Adverse Events (AEs)
Outcome Time Frame
Day 56
Outcome Description
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.
Outcome Measure
CTCAE Grade 3/4 Adverse Events (AEs) attributed to infusion of Ossium HPC, Marrow
Outcome Time Frame
Day 28
Outcome Description
The time of death will be recorded for each expired patient.
Outcome Measure
Death
Outcome Time Frame
Day 56
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 28
Outcome Measure
Cumulative incidences of neutrophil engraftment
Outcome Description
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.
Outcome Time Frame
Day 56
Outcome Measure
Cumulative incidences of platelet recovery
Outcome Description
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.
Outcome Time Frame
Day 365
Outcome Measure
Cumulative incidence of disease relapses
Outcome Description
TRM is defined as death without evidence of disease progression or recurrence.
Outcome Time Frame
Day 100 and Day 365
Outcome Measure
Transplant-related mortality (TRM)
Outcome Description
aGVHD is defined as any skin, gastrointestinal or liver abnormalities fulfilling the criteria of grades II-IV or grades III-IV.
Outcome Time Frame
Day 100, Day 180, and Day 365
Outcome Measure
Cumulative incidences of acute (aGVHD) Graft Versus Host Disease
Outcome Description
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).
Outcome Time Frame
Day 100, Day 180, and Day 365
Outcome Measure
Cumulative incidences of chronic (cGVHD) Graft Versus Host Disease
Outcome Description
A clinically significant infection is defined as any microbiologic or radiographic infection for which antimicrobial therapy was administered.
Outcome Time Frame
Day 100 and Day 365
Outcome Measure
Incidence of clinically-significant infections
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Roberto Alejandro Sica
Investigator Email
asica@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Hematology (non-malignant)
Categories Mesh Debug
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- NEOPLASMS
Immune System --- IMMUNE SYSTEM DISEASES
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Blood & Bone Marrow Cancers --- MYELOPROLIFERATIVE DISORDERS
Blood Disorders --- ANEMIA
Blood & Bone Marrow Cancers --- MYELODYSPLASTIC SYNDROMES
MeSH Terms
PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
LEUKEMIA, MYELOID, ACUTE
LEUKEMIA, BIPHENOTYPIC, ACUTE
LEUKEMIA, B-CELL
LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE
ANEMIA, REFRACTORY, WITH EXCESS OF BLASTS
HODGKIN DISEASE
LYMPHOMA, T-CELL, CUTANEOUS
LEUKEMIA
HEMATOLOGIC DISEASES
LYMPHOMA
LEUKEMIA, LYMPHOID
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMIC AND LYMPHATIC DISEASES
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
LEUKEMIA, MYELOID
MYELOPROLIFERATIVE DISORDERS
BONE MARROW DISEASES
CHRONIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
ANEMIA, REFRACTORY
ANEMIA
MYELODYSPLASTIC SYNDROMES
LYMPHOMA, T-CELL
LYMPHOMA, NON-HODGKIN
BONE MARROW TRANSPLANTATION
FLUDARABINE PHOSPHATE
CYCLOPHOSPHAMIDE
MESNA
MELPHALAN
MYCOPHENOLIC ACID
FILGRASTIM
TISSUE TRANSPLANTATION
CELL- AND TISSUE-BASED THERAPY
BIOLOGICAL THERAPY
THERAPEUTICS
TRANSPLANTATION
SURGICAL PROCEDURES, OPERATIVE
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
ORGANIC CHEMICALS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS
ALKANESULFONATES
ALKANESULFONIC ACIDS
ALKANES
HYDROCARBONS, ACYCLIC
SULFHYDRYL COMPOUNDS
SULFUR COMPOUNDS
SULFONIC ACIDS
SULFUR ACIDS
PHENYLALANINE
AMINO ACIDS, AROMATIC
AMINO ACIDS, CYCLIC
AMINO ACIDS
AMINO ACIDS, PEPTIDES, AND PROTEINS
CAPROATES
ACIDS, ACYCLIC
CARBOXYLIC ACIDS
FATTY ACIDS
LIPIDS
GRANULOCYTE COLONY-STIMULATING FACTOR
COLONY-STIMULATING FACTORS
GLYCOPROTEINS
GLYCOCONJUGATES
CARBOHYDRATES
HEMATOPOIETIC CELL GROWTH FACTORS
CYTOKINES
INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS
PEPTIDES
PROTEINS
BIOLOGICAL FACTORS